DU Yan-ming,CUI Li-wei,TAN Jing-yu,et al.Effect of triptolide on proliferation, migration and invasion of gastric cancer cells and its mechanism[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(07):595-599.
DU Yan-ming,CUI Li-wei,TAN Jing-yu,et al.Effect of triptolide on proliferation, migration and invasion of gastric cancer cells and its mechanism[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(07):595-599. DOI: 10.11659/jjssx.05E024103.
Effect of triptolide on proliferation, migration and invasion of gastric cancer cells and its mechanism
To explore the effects of triptolide (TPL) on the proliferation,migration and invasion of gastric cancer cells and its mechanism.
Methods
2
Human gastric cancer cell line MKN45 was cultured in vitro and treated with different concentrations of TPL for 48 hours.The cell proliferation inhibition rate was detected by CCK-8 method and the optimal concentration was selected for subsequent experiments.qRT-PCR was used to detect the expression of miR-29b and KDM2A mRNA in cells treated with different concentrations of TPL.MKN45 cells at logarithmic growth phase were randomly divided into the control group (without any treatment),the TPL group (treated with 200 μg/mL TPL),the inhibitor-NC+TPL group (transfected with inhibitor-NC and then treated with 200 μg/mL TPL),and the miR-29b inhibitor+TPL group (transfected with miR-29b inhibitor and then treated with 200 μg/mL TPL).qRT-PCR was used to detect the expression of miR-29b and KDM2A mRNA in each group of cells,and Western blot was used to detect the expression of KDM2A protein.The clone formation ability of each group of cells was detected by plate clone formation assay,and the migration and invasion abilities of each group of cells were detected by Transwell assay.
Results
2
TPL at concentrations of 25 μg/mL,50 μg/mL,100 μg/mL,and 200 μg/mL could significantly inhibit the proliferation of MKN45 cells (
P
<
0.05),up-regulate the expression of miR-29b in cells (
P
<
0.05),and down-regulate the expression of KDM2A mRNA (
P
<
0.05).The effect was most obvious at the concentration of 200 μg/mL,so 200 μg/mL TPL was selected for the subsequent experiments.Compared with the control group,the expression of miR-29b in the TPL group increased (
P
<
0.05),the expression of KDM2A mRNA and protein decreased (
P
<
0.05),and the numbers of clone formation,migration and invasion cells reduced (
P
<
0.05).Compared with the inhibitor-NC+TPL group,the expression of miR-29b in the miR-29b inhibitor+TPL group decreased (
P
<
0.05),the expression of KDM2A mRNA and protein increased (
P
<
0.05),and the numbers o
f clone formation,migration and invasion cells increased (
P
<
0.05).
Conclusion
2
TPL can inhibit the proliferation,migration and invasion of gastric cancer cells,and its mechanism is related to the regulation of the miR-29b/KDM2A signaling pathway.
关键词
Keywords
references
Miller KD , Nogueira L , Devasia T , et al . Cancer treatment and survivorship statistics,2022 [J]. CA Cancer J Clin , 2022 , 72 ( 5 ): 409 - 436 . doi: 10.3322/caac.21731 http://dx.doi.org/10.3322/caac.21731 .
Liang H , Che W , Peng F , et al . Triptolide inhibits esophageal squamous cell carcinoma progression by regulating the circNOX4/miR-153-3p/ SATB1 signaling pathway [J]. Thorac Cancer , 2024 , 15 ( 7 ): 538 - 549 . doi: 10.1111/1759-7714.15215 http://dx.doi.org/10.1111/1759-7714.15215 .
Jiang J , Song X , Yang J , et al . Triptolide inhibits proliferation and migration of human neuroblastoma SH-SY5Y cells by upregulating microRNA-181a [J]. Oncol Res , 2018 , 26 ( 8 ): 1235 - 1243 . doi: 10.3727/096504018X15179661552702 http://dx.doi.org/10.3727/096504018X15179661552702 .
Guo X , Chen J , Gao R , et al . Curcumin inhibits cervical cancer cell proliferation,migration and invasion by suppressing the PI3K/AKT signaling pathway via the miR-29b/KDM2A axis [J]. J Chin Pharm Sci , 2020 , 29 ( 6 ): 398 - 410 . doi: 10.5246/jcps.2020.06.038 http://dx.doi.org/10.5246/jcps.2020.06.038 .
Zhao Y , Chen X , Jiang J , et al . Epigallocatechin gallate reverses gastric cancer by regulating the long noncoding RNA LINC00511/miR-29b/KDM2A axis [J]. Biochim Biophys Acta Mol Basis Dis , 2020 , 1866 ( 10 ): 165856 . doi: 10.1016/j.bbadis.2020.165856 http://dx.doi.org/10.1016/j.bbadis.2020.165856 .
Kong Y , Zou S , Yang F , et al . RUNX3-mediated up-regulation of miR-29b suppresses the proliferation and migration of gastric cancer cells by targeting KDM2A [J]. Cancer Lett , 2016 , 381 ( 1 ): 138 - 148 . doi: 10.1016/j.canlet.2016.07.038 http://dx.doi.org/10.1016/j.canlet.2016.07.038 .
Cao W , Chen HD , Yu YW , et al . Changing profiles of cancer burden worldwide and in China:a secondary analysis of the global cancer statistics 2020 [J]. Chin Med J (Engl) , 2021 , 134 ( 7 ): 783 - 791 . doi: 10.1097/CM9.0000000000001474 http://dx.doi.org/10.1097/CM9.0000000000001474 .
Zhang Y , Lou Y , Wang J , et al . Research status and molecular mechanism of the traditional Chinese medicine and antitumor therapy combined strategy based on tumor microenvironment [J]. Front Immunol , 2021 , 11 ( 1 ): 609705 . doi: 10.3389/fimmu.2020.609705 http://dx.doi.org/10.3389/fimmu.2020.609705 .
Huang WJ , Ruan S , Wen F , et al . Multidrug resistance of gastric cancer:the mechanisms and Chinese medicine reversal agents [J]. Cancer Manag Res , 2020 , 12 ( 1 ): 12385 - 12394 . doi: 10.2147/CMAR.S274599 http://dx.doi.org/10.2147/CMAR.S274599 .
Chang W , Wang J , You Y , et al . Triptolide reduces neoplastic progression in hepatocellular carcinoma by downregulating the lipid lipase signaling pathway [J]. Cancers (Basel) , 2024 , 16 ( 3 ): 550 . doi: 10.3390/cancers16030550 http://dx.doi.org/10.3390/cancers16030550 .
Wu Q , Leng X , Ma X , et al . Triptolide reduces MDA-MB-231 cell metastasis by attenuating epithelial-mesenchymal transition through the ROCK/PTEN/Akt axis [J]. Chem Biodivers , 2023 , 20 ( 12 ): e202300399 . doi: 10.1002/cbdv.202300399 http://dx.doi.org/10.1002/cbdv.202300399 .
Wang T , Hou J , Jian S , et al . miR-29b negatively regulates MMP2 to impact gastric cancer development by suppress gastric cancer cell migration and tumor growth [J]. J Cancer , 2018 , 9 ( 20 ): 3776 - 3786 . doi: 10.7150/jca.26263 http://dx.doi.org/10.7150/jca.26263 .
Kimura Y , Ohzawa H , Kaneko Y , et al . Intraperitoneal transfer of miR-29b containing exosome suppresses the development of peritoneal metastases from gastric cancer [J]. Gan To Kagaku Ryoho , 2023 , 50 ( 13 ): 1435 - 1437 .
Li H , Liu G , Pan K , et al . Methylation-induced downregulation and tumor suppressive role of microRNA-29b in gastric cancer through targeting LASP1 [J]. Oncotarget , 2017 , 8 ( 56 ): 95880 - 95895 . doi: 10.18632/oncotarget.21431 http://dx.doi.org/10.18632/oncotarget.21431 .