PGRMC1介导的肝癌细胞自噬降低<sup>125</sup>I粒子辐射敏感性

刘平平; 王琛禹; 肖云华; 何闯; 熊俊儒; 邓良余; 黄学全

doi:10.16016/j.2097-0927.202311143

您当前的位置：

首页 >

文章列表页 >

PGRMC1介导的肝癌细胞自噬降低¹²⁵I粒子辐射敏感性

基础医学 | 更新时间：2026-01-09

- PGRMC1介导的肝癌细胞自噬降低¹²⁵I粒子辐射敏感性
- PGRMC1-mediated autophagy decreases the sensitivity of hepatocellular carcinoma cells to ¹²⁵I particle irradiation
- 陆军军医大学学报 2024年46卷第9期页码：1015-1023
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)第一附属医院核医学科
- 作者简介：
  
  [ 黄学全，E-mail: hxuequan@163.com HUANG Xuequan, E-mail: hxuequan@163.com
- 基金信息：
  
  重庆市自然科学基金面上项目(CSTB2022NSCQ-MSX1501);利益冲突声明所有作者声明不存在利益冲突;作者贡献声明刘平平、黄学全负责论文的设计、撰写、修改；王琛禹、肖云华、何闯、熊俊儒、邓良余负责实验操作及数据整理
- DOI：10.16016/j.2097-0927.202311143
  中图分类号： R730.23;R730.55;R735.7
- 收稿：2023-11-28，
  
  修回：2024-01-16，
  
  纸质出版：2024-05-15
- 稿件说明：
移动端阅览
刘平平, 王琛禹, 肖云华, 等. PGRMC1介导的肝癌细胞自噬降低¹²⁵I粒子辐射敏感性[J]. 陆军军医大学学报, 2024,46(9):1015-1023.

Pingping LIU, Chenyu WANG, Yunhua XIAO, et al. PGRMC1-mediated autophagy decreases the sensitivity of hepatocellular carcinoma cells to ¹²⁵I particle irradiation[J]. Journal of Army Medical University, 2024, 46(9): 1015-1023.
刘平平, 王琛禹, 肖云华, 等. PGRMC1介导的肝癌细胞自噬降低¹²⁵I粒子辐射敏感性[J]. 陆军军医大学学报, 2024,46(9):1015-1023. DOI： 10.16016/j.2097-0927.202311143.

Pingping LIU, Chenyu WANG, Yunhua XIAO, et al. PGRMC1-mediated autophagy decreases the sensitivity of hepatocellular carcinoma cells to ¹²⁵I particle irradiation[J]. Journal of Army Medical University, 2024, 46(9): 1015-1023. DOI： 10.16016/j.2097-0927.202311143.

摘要

目的

探究孕激素受体膜组分1(progesterone receptor membrane component 1，PGRMC1)介导的自噬对

125

I粒子照射肝癌细胞辐射敏感性的影响。

方法

肝癌细胞Huh7和LM3分别暴露于不同剂量(0、2、4、6、8 Gy)的

125

I粒子，利用透射电镜观察细胞自噬情况。使用自噬抑制剂氯喹(chloroquine，CQ)、激动剂雷帕霉素(rapam

ycin，Rapa)和PGRMC1抑制剂AG-205验证PGRMC1介导的自噬在肝癌细胞对

125

I粒子照射敏感性中的作用。利用CCK-8、克隆形成实验、流式细胞术检测细胞增殖、集落形成及凋亡情况，Western blot检测细胞中PGRMC1、微管相关蛋白轻链3-Ⅰ(microtubule-associated protein light chain 3-Ⅰ，LC3-Ⅰ)、LC3-Ⅱ和p62相对表达量。

结果

不同剂量

125

I粒子照射后Huh7和LM3细胞增殖和克隆形成能力显著降低(

＜0.05)，细胞凋亡数显著增加(

＜0.01)，且呈剂量依赖性。与0 Gy组相比，6 Gy组Huh7和LM3细胞中LC3-Ⅱ/LC3-Ⅰ比值显著增加(

＜0.01)，p62表达显著下调(

＜0.01)。与6 Gy组相比，6 Gy+CQ组Huh7和LM3细胞增殖能力和克隆形成数显著下降(

＜0.05)，细胞凋亡显著增加(

＜0.05)，而6 Gy+Rapa组上述结果则相反。与6 Gy组相比，6 Gy+AG205组Huh7和LM3细胞LC3-Ⅱ/LC3-Ⅰ比值显著降低(

＜0.05)，p62表达显著上调(

＜0.05)，细胞增殖能力和克隆形成数显著降低(

＜0.01)，细胞凋亡显著增加(

＜0.01)，而6 Gy+PGRMC1组上述结果则相反。

结论

125

I粒子照射诱导的PGRMC1升高可促进细胞自噬，从而增加肝癌细胞的增殖及克隆形成能力，减少肝癌细胞的凋亡。

Abstract

Objective

To investigate the effect of progesterone receptor membrane component 1 (PGRMC1) mediated autophagy on the sensitivity of liver cancer cells to

125

I particles irradiation.

Methods

Hepatoma cell lines Huh7 and LM3 were exposed to different doses (0

6 and 8 Gy) of

125

I particles

and cell autophagy was observed by transmission electron microscopy (TEM). Then

autophagy inhibitor chloroquine (CQ)

agonist rapamycin (Rapa)

and PGRMC1 inhibitor AG-205 were used respectively to verify that PGRMC1-mediated autophagy plays a key role in the sensitivity of hepatocellular carcinoma cells to

125

I particle irradiation. Cell proliferation

colony formation and apoptosis were detected by CCK-8 assay

clonal formation test and flow cytometry

respectively. The expression levels of PGRMC1

microtubule-associated protein light chain 3-Ⅰ (LC3-Ⅰ)

LC3-Ⅱ and p62 were detected by Western blotting.

Results

Different doses of

125

I particles irradiation significantly decreased the proliferation and clonogenesis of Huh7 and LM3 cells (

0.05)

and increased the apoptotic cells (

0.01)

in a dose-dependent manner. Compared with the 0 Gy group

the ratio of LC3-Ⅱ/ LC3-Ⅰ in Huh7 and LM3 cells was obviously increased

and the expression of p62 was significantly down-regulated in the 6 Gy group. The proliferation capacity and clonal formation ability of Huh7 and LM3 cells were decreased significantly

and their apoptotic cells were increased notably in the 6 Gy+CQ group than the 6 Gy group

while the above results were on the contrary in the 6 Gy+Rapa group. The 6 Gy+AG205 group had notably decreased LC3-Ⅱ/LC3-Ⅰ ratio in the Huh7 and LM3 cells

up-regulated p62 expression

reduced cell proliferation capacity and clone formation ability

and enhanced cell apoptosis when compared with the 6 Gy group

and the above results of the 6 Gy+PGRMC1 group were opposite.

Conclusion

Increment of PGRMC1 induced by

125

I irradiation can promote autophagy

increase the proliferation and clonogenesis

and reduce the apoptosis in hepatocellular carcinoma cells.

关键词

Keywords

references

黎欣怡, 阚雪锋, 郑传胜. 危险部位肝癌的射频消融治疗进展[J]. 临床放射学杂志, 2023, 42(10): 1699-1702. DOI: 10.13437/j.cnki.jcr.2023.10.012.

LI X Y, KAN X F, ZHENG C S. Progress in radio frequency ablation of liver cancer in dangerous sites[J]. J Clin Radiol, 2023, 42(10): 1699-1702. DOI: 10.13437/j.cnki.jcr.2023.10.012.

CHENG K, CAI N, ZHU J H, et al . Tumor-associated macrophages in liver cancer: from mechanisms to therapy[J ] . Cancer Commun, 2022, 42(11): 1112-1140. DOI: 10.1002/cac2.12345.

LV Y H, LV Y, WANG Z, et al . FLASH radiotherapy: a promising new method for radiotherapy[J ] . Oncol Lett, 2022, 24(6): 419. DOI: 10.3892/ol.2022.13539.

SANUKI N, TAKEDA A, TSURUGAI Y, et al . Role of stereotactic body radiotherapy in multidisciplinary management of liver metastases in patients with colorectal cancer[J ] . Jpn J Radiol, 2022, 40(10): 1009-1016. DOI: 10.1007/s11604-022-01307-9.

黄斯琪, 宁厚法, 崔新江, 等. 125 I粒子植入术联合化疗治疗72例不可切除晚期胰腺癌临床观察[J ] . 中华肿瘤防治杂志, 2020, 27(17): 1415-1420. DOI: 10.16073/j.cnki.cjcpt.2020.17.10.

HUANG S Q, NING H F, CUI X J, et al . Clinical effectiveness of 125 I radioactive particle implantation combined with chemotherapy in the treatment for unresectable advanced pancreatic carcinoma[J ] . Chin J Cancer Prev Treat, 2020, 27(17): 1415-1420. DOI: 10.16073/j.cnki.cjcpt.2020.17.10..

TERRAPON A P R, KRVGER M, HUNDSBERGER T, et al . Laser interstitial thermal therapy for radionecrosis[J ] . Neurosurg Clin N Am, 2023, 34(2): 209-225. DOI: 10.1016/j.nec.2022.11.001.

XU Z, XU M L, LI M, et al . Effects of I125 seed stent implantation combined with arterial infusion chemoembolization on tumor markers, p53 expression, and prognosis in patients with cholangiocarcinoma[J ] . Bioengineered, 2022, 13(2): 2943-2950. DOI: 10.1080/21655979.2021.2022263.

HE Y, DONG X H, ZHU Q, et al . Ultrasound- triggered microbubble destruction enhances the radiosensitivity of glioblastoma by inhibiting PGRMC1-mediated autophagy in vitro and in vivo [J ] . Mil Med Res, 2022, 9(1): 9. DOI: 10.1186/s40779-022-00369-0..

ZHU X F, JI M D, HAN Y, et al . PGRMC1-dependent autophagy by hyperoside induces apoptosis and sensitizes ovarian cancer cells to cisplatin treatment[J ] . Int J Oncol, 2017, 50(3): 835-846. DOI: 10.3892/ijo.2017.3873.

LI F S, XU J, ZHU Y, et al . Analysis of cells proliferation and microRNAs expression profile in human chondrosarcoma SW1353 cells exposed to iodine-125 seeds irradiation[J ] . Dose Response, 2020, 18(2): 1559325820920525. DOI: 10.1177/1559325820920525.

赵东艳, 周蓉, 祝巧娟, 等. 碘125粒子植入治疗胰腺癌的现状[J]. 中外医学研究, 2023, 21(2): 172-176. DOI: 10.14033/j.cnki.cfmr.2023.02.043.

ZHAO D Y, ZHOU R, ZHU Q J, et al . Current status of iodine-125 seeds implantation in the treatment of pancreatic cancer[J ] . Chin Foreign Med Res, 2023, 21(2): 172-176. DOI: 10.14033/j.cnki.cfmr.2023.02.043.

VILAR TABANERA A, AJURIA O, RIOJA M E, et al . Selective neck dissection guided by a radioactive I125 seed for papillary thyroid carcinoma recurrence[J ] . Cir Esp, 2020, 98 (8): 478-481. DOI: 10.1016/j.ciresp.2020.04.018.

WANG C, LI T K, ZENG C H, et al . Inhibition of endoplasmic reticulum stress-mediated autophagy enhances the anticancer effect of iodine-125 seed radiation on esophageal squamous cell carcinoma[J ] . Radiat Res, 2020, 194(3): 236-245. DOI: 10.1667/RADE-20-00057.1.

TAKABAYASHI K, KASHIWAGI K, KAWATA T, et al . Continuous low-dose irradiation by I-125 seeds induces apoptosis of gastric cancer cells regardless of histological origin[J ] . Cancer Biol Ther, 2014, 15(1): 81-88. DOI: 10.4161/cbt.26610.

ZOU L, CHANG W, BAI J H, et al . Iodine-125 induced cholangiocarcinoma cell death is enhanced by inhibition of endoplasmic reticulum stress-mediated protective autophagy[J ] . Neoplasma, 2022, 69(3): 620-629. DOI: 10.4149/neo_2022_211102N1556.

党中峰, 马亚兵, 张淯泉, 等. 调控自噬相关通路对肿瘤治疗的研究进展[J]. 甘肃医药, 2023, 42(9): 773-775, 782. DOI: 10.15975/j.cnki.gsyy.2023.09.002.

DANG Z F, MA Y B, ZHANG Y Q, et al . Modulation of autophagy-related pathways on tumor therapy[J ] . Gansu Med J, 2023, 42(9): 773-775, 782. DOI: 10.15975/j.cnki.gsyy.2023.09.002.

FAN S J, YUE L Y, WAN W, et al . Inhibition of autophagy by a small molecule through covalent modification of the LC3 protein[J ] . Angew Chem Int Ed, 2021, 60(50): 26105-26114. DOI: 10.1002/anie.202109464.

YOU J H, LEE J, ROH J L. PGRMC1-dependent lipophagy promotes ferroptosis in paclitaxel-tolerant persister cancer cells[J]. J Exp Clin Cancer Res, 2021, 40(1): 350. DOI: 10.1186/s13046-021-02168-2.

SOLAIRAJA S, RAMALINGAM S, DUNNA N R, et al . Progesterone receptor membrane component 1 and its accomplice: emerging therapeutic targets in lung cancer[J ] . Endocr Metab Immune Disord Drug Targets, 2022, 22(6): 601-611. DOI: 10.2174/1871530321666211130145542.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

AKT1介导的肝癌细胞自噬增强¹²⁵I粒籽辐照敏感性

载脂蛋白E拟肽COG1410对蛛网膜下腔出血后自噬和凋亡的影响

吉西他滨诱导膀胱癌T24细胞自噬的实验研究

热习服对热射病小鼠中枢神经细胞自噬及凋亡的影响

索拉非尼诱导肝癌HepG2细胞自噬的机制及意义

PGRMC1介导的肝癌细胞自噬降低125I粒子辐射敏感性

PGRMC1-mediated autophagy decreases the sensitivity of hepatocellular carcinoma cells to 125I particle irradiation

DOI：10.16016/j.2097-0927.202311143

摘要

Abstract

关键词

Keywords

references

PGRMC1介导的肝癌细胞自噬降低¹²⁵I粒子辐射敏感性

PGRMC1-mediated autophagy decreases the sensitivity of hepatocellular carcinoma cells to ¹²⁵I particle irradiation