Preparation of nanosized hypoxia-inducible factor 1α inhibitor and its application in reversing chemoresistance in colorectal cancer cells

ZHENG Chuanhao; DAN Ruijue; XI Xi; YING Wang; LUO Qiang

doi:10.16016/j.2097-0927.202502006

您当前的位置：

首页 >

文章列表页 >

Preparation of nanosized hypoxia-inducible factor 1α inhibitor and its application in reversing chemoresistance in colorectal cancer cells

Basic Medicine | 更新时间：2025-06-11

- Preparation of nanosized hypoxia-inducible factor 1α inhibitor and its application in reversing chemoresistance in colorectal cancer cells
- Journal of Army Medical University Vol. 47, Issue 11, Pages: 1177-1189(2025)
- 作者机构：
  
  陆军军医大学（第三军医大学）第二附属医院消化内科，重庆
- 作者简介：
- 基金信息：
  
  the General Project of Natural Science Foundation of Chongqing(CSTB2022NSCQ-MSX1336)
- DOI：10.16016/j.2097-0927.202502006
  CLC： R735.35;R914.2;R979.19
- Received：14 February 2025，
  
  Revised：15 April 2025，
  
  Accepted：16 April 2025，
  
  Published：15 June 2025
- 稿件说明：
移动端阅览
郑传浩，但瑞珏，奚茜，等.缺氧诱导因子-1α纳米抑制剂的构建及在逆转结直肠癌细胞化疗耐药中的应用［J］.陆军军医大学学报，2025，47（11）：1177-1189.DOI：10.16016/j.2097-0927.202502006.

ZHENG C H，DAN R J，XI X，et al.Preparation of nanosized hypoxia-inducible factor 1α inhibitor and its application in reversing chemoresistance in colorectal cancer cells［J］.J Army Med Univ，2025，47（11）：1177-1189.DOI：10.16016/j.2097-0927.202502006.
郑传浩，但瑞珏，奚茜，等.缺氧诱导因子-1α纳米抑制剂的构建及在逆转结直肠癌细胞化疗耐药中的应用［J］.陆军军医大学学报，2025，47（11）：1177-1189.DOI：10.16016/j.2097-0927.202502006. DOI：

ZHENG C H，DAN R J，XI X，et al.Preparation of nanosized hypoxia-inducible factor 1α inhibitor and its application in reversing chemoresistance in colorectal cancer cells［J］.J Army Med Univ，2025，47（11）：1177-1189.DOI：10.16016/j.2097-0927.202502006. DOI：

摘要

目的

对缺氧诱导因子-1α（hypoxia-inducible factor 1α， HIF-1α）抑制剂YC-1进行纳米化改性，探究其在逆转结直肠癌化疗耐药中的作用。

方法

利用YC-1分子中的活性官能团羟基（-OH）与甲氧基聚乙二醇-羧酸的羧基（methoxy-polyethylene glycol carboxylic acid， mPEG

350

-COOH）缩合反应构建纳米抑制剂mPEG

350

-YC-1 （MYC-1），并通过核磁共振氢谱（

H nuclear magnetic resonance，

H-NMR）进行验证；利用透射电子显微镜（transmission electron microscope， TEM）分析其形貌，利用动态光散射（dynamic light scattering， DLS）分析其粒径分布情况；通过将FITC标记的MYC-1 （FYC-1）与HCT15细胞相互作用，利用激光共聚焦显微镜观察细胞对FYC-1的摄取能力；CCK-8实验检测MYC-1的细胞毒性；通过耐药HCT15细胞（resistant-HCT15， R-HCT15）的毒性实验和活/死细胞染色检测MYC-1对化疗药物5-氟尿嘧啶（5-fluorouracil，5-Fu）的增敏效果；采用免疫荧光染色和Western blot实验来检测MYC-1逆转耐药的机制。构建小鼠R-HCT15皮下移植瘤模型，采用简单随机分组法将小鼠分为PBS（

=3）、5-Fu（

=3）、MYC-1（

=3）和MYF（

=3）组。通过绘制肿瘤体积增长曲线，测量完成疗效评估当日的小鼠肿瘤质量，对比各组小鼠肿瘤生长情况，从而评价MYC-1逆转结直肠癌对5-Fu耐药的能力。

结果

成功制备了纳米抑制剂MYC-1，通过TEM和DLS验证MYC-1在水相溶液中能自组装成直径约为（19.96±2.97） nm的纳米颗粒。成功制备FYC-1，将FYC-1与HCT15细胞相互作用，FYC-1能更好地被细胞摄取，表明两亲性的MYC-1具有更强的内吞入胞能力；MYC-1与5-Fu联合作用于R-HCT15结肠癌细胞，其耐药指数（resistant index， RI）由7.99下降到1.55，耐药指数的相对逆转率（relative reversal rate， RRR）为80.60%；活/死细胞染色显示，MYC-1能增加5-Fu对R-HCT15细胞的毒性；免疫荧光染色和Western blot实验表明MYC-1能够有效抑制HIF-1α在胞内的表达（

0.01）；MYC-1与5-Fu联合作用于R-HCT15皮下移植瘤小鼠，与PBS（

0.001）、5-Fu（

0.01）和MYC-1（

0.01）比较，MYF组治疗效果最佳；肿瘤组织HIF-1α免疫荧光染色显示，MYC-1和MYF组HIF-1α表达下降；小鼠重要脏器HE染色显示，各治疗组重要脏器未见明显损害。

结论

MYC-1纳米抑制剂能够通过降低结直肠癌细胞HIF-1α蛋白的表达，从而逆转结直肠癌对于5-Fu化疗的耐药性，有效改善5-Fu的治疗效果。

Abstract

‍Objective‍　‍To modify YC-1

an inhibitor of hypoxia-inducible factor-1α (HIF-1α) into nanoparticles and explore its effect on reversing chemoresistance of colorectal cancer cells. Methods‍　‍Nano-inhibitor mPEG

350

-YC-1 (MYC-1) was prepared by the carboxyl condensation reaction of the active functional group hydroxyl (-OH) in the YC-1 molecule with methoxy polyethylene glycol carboxylic acid

and was verified by

H nuclear magnetic resonance (

H-NMR). Its morphology was analyzed by transmission electron microscope (TEM)

and its particle size distribution was analyzed by dynamic light scattering (DLS). By interacting FITC-labeled MYC-1 (FYC-1) with HCT15 cells

the uptake ability of FYC-1 by the cells was observed using laser confocal microscopy. The cytotoxicity of MYC-1 was measured with CCK-8 assay. The sensitization effect of MYC-1 on the chemotherapy drug 5-Fu was detected through toxicity tests of resistant HCT15 cells (resistant HCT15

R-HCT15) and live/dead cell staining. The mechanism of MYC-1 reversing drug resistance was determined with immunofluorescence staining of HIF-1α and western blotting. Finally

a subcutaneous transplanted tumor model of R-HCT15 cells was constructed. The tumor bearing mice were randomly divided into PBS

5-Fu

MYC-1

and MYF groups

with 3 mice in each group. The tumor volume and weight were observed after treatment in each group to evaluate the ability of MYC-1 to reverse 5-Fu resistance in colorectal cancer. Results‍　‍The nano-inhibitor MYC-1 was successfully prepared. TEM and DLS showed that MYC-1 could self-assemble into nanoparticles with a diameter of approximately 19.96±2.97 nm in aqueous solution. FYC-1 was also successfully prepared. When FYC-1 was interacted with HCT15 cells

FYC-1 could be better taken up by the cells

indicating that the amphiphilic MYC-1 could

be better endocytosed into the cells to exert its function. When MYC-1 and 5-Fu acted in combination in colon cancer R-HCT15 cells

the resistance index (RI) was decreased from 7.99 to 1.55

and the relative reversal rate (RRR) of RI was 80.6%. Live (green)/dead (red) cell staining revealed that MYC-1 increased the toxicity of 5-Fu to R-HCT15 cells. Immunofluorescence staining (

0.01) and Western blotting indicated that MYC-1 effectively inhibited the intracellular expression of HIF-1α. The combined action of MYC-1 and 5-Fu on mice with R-HCT15 subcutaneous transplanted tumors had the best therapeutic effect when compared with PBS (

0.001)

5-Fu (

0.01)

and MYC-1 (

0.01). Immunofluorescence staining of HIF-1α in tumor tissues displayed that the expression of HIF-1α was decreased in the MYC-1 and MYF groups. HE staining showed that there was no obvious damage to the important organs in each treatment group. Conclusion‍　‍Nano-inhibitor MYC-1 can reverse the drug resistance of colorectal cancer to 5-Fu chemotherapy by reducing the expression of HIF-1α protein in colorectal cancer cells

thereby effectively improving the therapeutic effect of 5-Fu.

关键词

Keywords

references

YANG Y ， LIU Q Y ， WANG M ， et al . Genetically programmable cell membrane-camouflaged nanoparticles for targeted combination therapy of colorectal cancer ［J］. Signal Transduct Target Ther ， 2024 ， 9 （ 1 ）： 158 . DOI： 10.1038/s41392-024-01859-4 http://dx.doi.org/10.1038/s41392-024-01859-4 .

DEKKER E ， TANIS P J ， VLEUGELS J L A ， et al . Colorectal cancer ［J］. Lancet ， 2019 ， 394 （ 10207 ）： 1467 - 1480 . DOI： 10.1016/S0140-6736（19）32319-0 http://dx.doi.org/10.1016/S0140-6736（19）32319-0 .

BILLER L H ， SCHRAG D . Diagnosis and treatment of metastatic colorectal cancer ［J］. Jama ， 2021 ， 325 （ 7 ）： 669 . DOI： 10.1001/jama.2021.0106 http://dx.doi.org/10.1001/jama.2021.0106 .

FRIEBE A ， KOESLING D . Regulation of nitric oxide-sensitive guanylyl cyclase ［J］. Circ Res ， 2003 ， 93 （ 2 ）： 96 - 105 . DOI： 10.1161/01.res.0000082524.34487.31 http://dx.doi.org/10.1161/01.res.0000082524.34487.31 .

孙燕，王灵巧，张国伟，等 . ACSS2介导的上皮间质转化在乙醇促结直肠癌细胞迁移中的作用及机制［J］. 陆军军医大学学报， 2023 ， 45 （ 17 ）： 1806 - 1818 . DOI： 10.16016/j.2097-0927.202303141 http://dx.doi.org/10.16016/j.2097-0927.202303141 .

SUN Y ， WANG L Q ， ZHANG G W ， et al . Role and mechanism of ACSS2-mediated epithelial-mesenchymal transition in ethanol-promoted migration of colorectal cancer ［J］. J Army Med Univ ， 2023 ， 45 （ 17 ）： 1806 - 1818 . DOI： 10.16016/j.2097-0927.202303141 http://dx.doi.org/10.16016/j.2097-0927.202303141 .

LI N ， LU B ， LUO C Y ， et al . Incidence， mortality， survival， risk factor and screening of colorectal cancer： a comparison among China， Europe， and northern America ［J］. Cancer Lett ， 2021 ， 522 ： 255 - 268 . DOI： 10.1016/j.canlet.2021.09.034 http://dx.doi.org/10.1016/j.canlet.2021.09.034 .

QU R Z ， MA Y P ， ZHANG Z P ， et al . Increasing burden of colorectal cancer in China ［J］. Lancet Gastroenterol Hepatol ， 2022 ， 7 （ 8 ）： 700 . DOI： 10.1016/S2468-1253（22）00156-X http://dx.doi.org/10.1016/S2468-1253（22）00156-X .

杨思琦，段家翔，李小东，等 . 腹腔镜结直肠癌根治术的手术时段对患者术后康复的影响［J］. 陆军军医大学学报， 2023 ， 45 （ 4 ）： 301 - 306 . DOI： 10.16016/j.2097-0927.202207165 http://dx.doi.org/10.16016/j.2097-0927.202207165 .

YANG S Q ， DUAN J X ， LI X D ， et al . Effect of different periods of laparoscopic radical resection for colorectal cancer on rehabilitation： report of 190 cases ［J］. J Army Med Univ ， 2023 ， 45 （ 4 ）： 301 - 306 . DOI： 10.16016/j.2097-0927.202207165 http://dx.doi.org/10.16016/j.2097-0927.202207165 .

VODENKOVA S ， BUCHLER T ， CERVENA K ， et al . 5-fluorouracil and other fluoropyrimidines in colorectal cancer： Past， present and future ［J］. Pharmacol Ther ， 2020 ， 206 ： 107447 . DOI： 10.1016/j.pharmthera.2019.107447 http://dx.doi.org/10.1016/j.pharmthera.2019.107447 .

YANG L ， YANG J L ， KLEPPE A ， et al . Personalizing adjuvant therapy for patients with colorectal cancer ［J］. Nat Rev Clin Oncol ， 2023 ， 21 （ 1 ）： 67 - 79 . DOI： 10.1038/s41571-023-00834-2 http://dx.doi.org/10.1038/s41571-023-00834-2 .

SCHMOLL H J . Development of treatment for advanced colorectal cancer： infusional 5-FU and the role of new agents ［J］. Eur J Cancer ， 1996 ， 32 A（ Suppl 5 ）： S18 - S22 . DOI： 10.1016/s0959-8049（96）00335-8 http://dx.doi.org/10.1016/s0959-8049（96）00335-8 .

LONGLEY D B ， HARKIN D P ， JOHNSTON P G . 5-fluorouracil： mechanisms of action and clinical strategies ［J］. Nat Rev Cancer ， 2003 ， 3 （ 5 ）： 330 - 338 . DOI： 10.1038/nrc1074 http://dx.doi.org/10.1038/nrc1074 .

TIRENDI S ， MARENGO B ， DOMENICOTTI C ， et al . Colorectal cancer and therapy response： a focus on the main mechanisms involved ［J］. Front Oncol ， 2023 ， 13 ： 1208140 . DOI： 10.3389/fonc.2023.1208140 http://dx.doi.org/10.3389/fonc.2023.1208140 .

SETHY C ， KUNDU C N . 5-Fluorouracil （5-FU） resistance and the new strategy to enhance the sensitivity against cancer： Implication of DNA repair inhibition ［J］. Biomed Pharmacother ， 2021 ， 137 ： 111285 . DOI： 10.1016/j.biopha.2021.111285 http://dx.doi.org/10.1016/j.biopha.2021.111285 .

SHUKLA S K ， PUROHIT V ， MEHLA K ， et al . MUC1 and HIF-1alpha signaling crosstalk induces anabolic glucose metabolism to impart gemcitabine resistance to pancreatic cancer ［J］. Cancer Cell ， 2017 ， 32 （ 1 ）： 71 - 87.e7 . DOI： 10.1016/j.ccell.2017.06.004 http://dx.doi.org/10.1016/j.ccell.2017.06.004 .

LEE K M ， GILTNANE J M ， BALKO J M ， et al . MYC and MCL1 cooperatively promote chemotherapy-resistant breast cancer stem cells via regulation of mitochondrial oxidative phosphorylation ［J］. Cell Metab ， 2017 ， 26 （ 4 ）： 633 - 647.e7 . DOI： 10.1016/j.cmet.2017.09.009 http://dx.doi.org/10.1016/j.cmet.2017.09.009 .

ERIN N ， GRAHOVAC J ， BROZOVIC A ， et al . Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance ［J］. Drug Resist Updat ， 2020 ， 53 ： 100715 . DOI： 10.1016/j.drup.2020.100715 http://dx.doi.org/10.1016/j.drup.2020.100715 .

SAATCI O ， KAYMAK A ， RAZA U ， et al . Targeting lysyl oxidase （LOX） overcomes chemotherapy resistance in triple negative breast cancer ［J］. Nat Commun ， 2020 ， 11 （ 1 ）： 2416 . DOI： 10.1038/s41467-020-16199-4 http://dx.doi.org/10.1038/s41467-020-16199-4 .

MASOUD G N ， LI W . HIF-1α pathway： role， regulation and intervention for cancer therapy ［J］. Acta Pharm Sin B ， 2015 ， 5 （ 5 ）： 378 - 389 . DOI： 10.1016/j.apsb.2015.05.007 http://dx.doi.org/10.1016/j.apsb.2015.05.007 .

MCALEESE C E ， CHOUDHURY C ， BUTCHER N J ， et al . Hypoxia-mediated drug resistance in breast cancers ［J］. Cancer Lett ， 2021 ， 502 ： 189 - 199 . DOI： 10.1016/j.canlet. 2020.11.045 http://dx.doi.org/10.1016/j.canlet.2020.11.045 .

杨婷，王廷睿，韩珊珊，等 . LINC00294通过AKT/mTOR/HIF-1a通路促进乳腺癌细胞的增殖、侵袭与迁移［J］. 陆军军医大学学报， 2023 ， 45 （ 18 ）： 1927 - 1936 . DOI： 10.16016/j.2097-0927.202303100 http://dx.doi.org/10.16016/j.2097-0927.202303100 .

YANG T ， WANG T R ， HAN S S ， et al . LINC00294 promotes proliferation， invasion， and migration of breast cancer cells via AKT/mTOR/HIF-1α pathway ［J］. J Army Med Univ ， 2023 ， 45 （ 18 ）： 1927 - 1936 . DOI： 10.16016/j.2097-0927.202303100 http://dx.doi.org/10.16016/j.2097-0927.202303100 .

FENG J ， LI J J ， WU L W ， et al . Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma ［J］. J Exp Clin Cancer Res ， 2020 ， 39 （ 1 ）： 126 . DOI： 10.1186/s13046-020-01629-4 http://dx.doi.org/10.1186/s13046-020-01629-4 .

RASHID M ， ZADEH L R ， BARADARAN B ， et al . Up-down regulation of HIF-1α in cancer progression ［J］. Gene ， 2021 ， 798 ： 145796 . DOI： 10.1016/j.gene.2021.145796 http://dx.doi.org/10.1016/j.gene.2021.145796 .

YEO E J ， CHUN Y S ， CHO Y S ， et al . YC-1： a potential anticancer drug targeting hypoxia-inducible factor 1 ［J］. J Natl Cancer Inst ， 2003 ， 95 （ 7 ）： 516 - 525 . DOI： 10.1093/jnci/95.7.516 http://dx.doi.org/10.1093/jnci/95.7.516 .

YEO E J ， CHUN Y S ， PARK J W . New anticancer strategies targeting HIF-1 ［J］. Biochem Pharmacol ， 2004 ， 68 （ 6 ）： 1061 - 1069 . DOI： 10.1016/j.bcp.2004.02.040 http://dx.doi.org/10.1016/j.bcp.2004.02.040 .

HE J N ， XIA K K ， ZHAO B G ， et al . Codelivery of high-molecular-weight poly-porphyrins and HIF-1α inhibitors for in vivo synergistic anticancer therapy ［J］. Biomacromo-lecules ， 2021 ， 22 （ 11 ）： 4783 - 4793 . DOI： 10.1021/acs.biomac.1c01073 http://dx.doi.org/10.1021/acs.biomac.1c01073 .

LANG J Y ， ZHAO X ， WANG X C ， et al . Targeted co-delivery of the iron Chelator deferoxamine and a HIF1α inhibitor impairs pancreatic tumor growth ［J］. ACS Nano ， 2019 ： acsnano. 8 b 08823 . DOI： 10.1021/acsnano.8b08823 http://dx.doi.org/10.1021/acsnano.8b08823 .

OUYANG C L ， ZHANG J ， LEI X Y ， et al . Advances in antitumor research of HIF-1α inhibitor YC-1 and its derivatives ［J］. Bioorg Chem ， 2023 ， 133 ： 106400 . DOI： 10.1016/j.bioorg.2023.106400 http://dx.doi.org/10.1016/j.bioorg.2023.106400 .

TRAYNOR K . Riociguat approved for pulmonary hypertension ［J］. Am J Health Syst Pharm ， 2013 ， 70 （ 22 ）： 1960 . DOI： 10.2146/news130073 http://dx.doi.org/10.2146/news130073 .

MARKHAM A ， DUGGAN S . Vericiguat： first approval ［J］. Drugs ， 2021 ， 81 （ 6 ）： 721 - 726 . DOI： 10.1007/s40265-021-01496-z http://dx.doi.org/10.1007/s40265-021-01496-z .

YU K H ， HUNG H Y . Synthetic strategy and structure-activity relationship （SAR） studies of 3-（5'-hydroxymethyl-2'-furyl）-1-benzyl indazole （YC-1， Lificiguat）： a review ［J］. RSC Adv ， 2021 ， 12 （ 1 ）： 251 - 264 . DOI： 10.1039/d1ra08120a http://dx.doi.org/10.1039/d1ra08120a .

KALTBEITZEL J ， WICH P R . Protein-based nanoparticles： from drug delivery to imaging， nanocatalysis and protein therapy ［J］. Angew Chem Int Ed ， 2023 ， 62 （ 44 ）： e202216097 . DOI： 10.1002/anie.202216097 http://dx.doi.org/10.1002/anie.202216097 .

VAN DER LAAN K ， HASANI M ， ZHENG T ， et al . Nanodiamonds for in vivo applications ［J］. Small ， 2018 ， 14 （ 19 ）： e1703838 . DOI： 10.1002/smll.201703838 http://dx.doi.org/10.1002/smll.201703838 .

ZHOU J R ， TIAN G ， ZENG L J ， et al . Nanoscaled metal-organic frameworks for biosensing， imaging， and cancer therapy ［J］. Adv Healthc Mater ， 2018 ， 7 （ 10 ）： e1800022 . DOI： 10.1002/adhm.201800022 http://dx.doi.org/10.1002/adhm.201800022 .

SUN Q ， HONG Z Y ， ZHANG C ， et al . Immune checkpoint therapy for solid tumours： clinical dilemmas and future trends ［J］. Signal Transduct Target Ther ， 2023 ， 8 （ 1 ）： 320 . DOI： 10.1038/s41392-023-01522-4 http://dx.doi.org/10.1038/s41392-023-01522-4 .

KARA G ， CALIN G A ， OZPOLAT B . RNAi-based therapeutics and tumor targeted delivery in cancer ［J］. Adv Drug Deliv Rev ， 2022 ， 182 ： 114113 . DOI： 10.1016/j.addr.2022.114113 http://dx.doi.org/10.1016/j.addr.2022.114113 .

ASHIQUE S ， GARG A ， HUSSAIN A ， et al . Nanodelivery systems： an efficient and target-specific approach for drug-resistant cancers ［J］. Cancer Med ， 2023 ， 12 （ 18 ）： 18797 - 18825 . DOI： 10.1002/cam4.6502 http://dx.doi.org/10.1002/cam4.6502 .

ZHAO Y ， XING C ， DENG Y T ， et al . HIF-1α signaling： Essential roles in tumorigenesis and implications in targeted therapies ［J］. Genes Dis ， 2023 ， 11 （ 1 ）： 234 - 251 . DOI： 10.1016/j.gendis.2023.02.039 http://dx.doi.org/10.1016/j.gendis.2023.02.039 .

CAO Y . Adipocyte and lipid metabolism in cancer drug resistance ［J］. J Clin Invest ， 2019 ， 129 （ 8 ）： 3006 - 3017 . DOI： 10.1172/jci127201 http://dx.doi.org/10.1172/jci127201 .

NIU X ， LIU W J ， ZHANG Y L ， et al . Cancer plasticity in therapy resistance： mechanisms and novel strategies ［J］. Drug Resist Updat ， 2024 ， 76 ： 101114 . DOI： 10.1016/j.drup.2024.101114 http://dx.doi.org/10.1016/j.drup.2024.101114 .

STADLER Z K ， MAIO A ， CHAKRAVARTY D ， et al . Therapeutic implications of germline testing in patients with advanced cancers ［J］. J Clin Oncol ， 2021 ， 39 （ 24 ）： 2698 - 2709 . DOI： 10.1200/JCO.20.03661 http://dx.doi.org/10.1200/JCO.20.03661 .

CHAN S L ， WONG A M ， LEE K ， et al . Personalized therapy for hepatocellular carcinoma： where are we now？［J］. Cancer Treat Rev ， 2016 ， 45 ： 77 - 86 . DOI： 10.1016/j.ctrv.2016.02.008 http://dx.doi.org/10.1016/j.ctrv.2016.02.008 .

SINICROPE F A ， OKAMOTO K ， KASI P M ， et al . Molecular biomarkers in the personalized treatment of colorectal cancer ［J］. Clin Gastroenterol Hepatol ， 2016 ， 14 （ 5 ）： 651 - 658 . DOI： 10.1016/j.cgh.2016.02.008 http://dx.doi.org/10.1016/j.cgh.2016.02.008 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Plateau hypoxia improves tumor immune microenvironment and inhibits subcutaneous tumor growth of colorectal cancer

Down-regulation of miR-4443/TIMP2 signaling pathway enhances sorafenib sensitivity in HepG2 cells

Role of stearoyl CoA desaturase 1 in resistance of colon cancer cells to 5-fluorouracil

Differential expression of MUC1 gene mediated by Fusobacterium nucleatum in colorectal cancer cells

Related Author

ZHAO Sijie

WANG Meng

GAO Yuan

YANG Fang

HU Shaofan

MIAO Hongming

XIAO Hanxi

ZHANG Yueting

Related Institution

Department of Pathophysiology， Key Laboratory of Extreme Environmental Medicine of Ministry of Education， Faculty of High Altitude Military Medicine， Army Medical University （Third Military Medical University）

Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University)

Department of Oncology, First Affiliated Hospital, Army Medical University (Third Military Medical University)

Department of Clinical Microbiology and Immunology, Faculty of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University),, .

Department of General Surgery, the Third Affiliated Hospital of Chongqing Medical University

⁰