Yuan Tein-Ming, Liu Bang-Hung, Huang Chih-Jou, Huang Yi-Ching, Chuang Show-Mei
Department of Surgery, Feng-Yuan Hospital, Ministry of Health and Welfare, Taichung, Taiwan.
Department of Dental Technology and Materials Science, Central Taiwan University of Science and Technology, Taichung, Taiwan.
SAGE Open Med. 2024 Oct 30;12:20503121241292673. doi: 10.1177/20503121241292673. eCollection 2024.
Understanding the role of TRIB3 in cellular chemotherapy responsiveness and survival could facilitate its development as a prognostic marker that could be used to improve chemotherapeutic efficiency against specific tumors. Therefore, the role of TRIB3 to reflect the cytotoxic abilities of chemotherapeutic agents was clarified in the tested gastric cancer cell lines.
We have comprehensively investigated the protein expression of TRIB3 in three gastric cancer cell lines AGS, TMK-1, and MKN-45 cells treated with the anticancer drugs, 5-fluorouracil, cisplatin, and docetaxel. The Cell Count kit-8 was used to evaluate cell viability. Immunoblotting was performed to assay protein levels after drug treatment. Flow cytometry was carried out to evaluate the levels of sub-G1 cell population.
Treatment of the tested gastric cancer cell lines dose-dependently decreased cell viability and protein levels of TRIB3 while increasing apoptosis. Overexpression of TRIB3 protects MKN-45 cells from endoplasmic reticulum stress-induced apoptosis but does not influence the induction of autophagy by anticancer drugs. In addition, overexpression of TRIB3 also rescued paroxetine-induced apoptosis and endoplasmic reticulum stress.
Our previous and present results indicate that TRIB3 can protect gastric cancer cells against anticancer drug treatment and that downregulating TRIB3 may increase these cells' sensitivity to anticancer drugs. We thus suggest that the capability of anticancer drugs to downregulate TRIB3 can indicate tumors' potential susceptibility to these drugs.
了解TRIB3在细胞化疗反应性和生存中的作用，有助于将其开发为一种预后标志物，用于提高针对特定肿瘤的化疗效率。因此，在受试的胃癌细胞系中阐明了TRIB3反映化疗药物细胞毒性能力的作用。
我们全面研究了TRIB3在三种胃癌细胞系AGS、TMK-1和MKN-45细胞中经抗癌药物5-氟尿嘧啶、顺铂和多西他赛处理后的蛋白表达。使用细胞计数试剂盒-8评估细胞活力。药物处理后进行免疫印迹分析蛋白水平。通过流式细胞术评估亚G1期细胞群体水平。
受试胃癌细胞系经处理后，细胞活力和TRIB3蛋白水平呈剂量依赖性降低，同时细胞凋亡增加。TRIB3的过表达可保护MKN-45细胞免受内质网应激诱导的凋亡，但不影响抗癌药物诱导的自噬。此外，TRIB3的过表达还可挽救帕罗西汀诱导的凋亡和内质网应激。
我们之前和现在的结果表明，TRIB3可保护胃癌细胞免受抗癌药物治疗，下调TRIB3可能会增加这些细胞对抗癌药物的敏感性。因此，我们认为抗癌药物下调TRIB3的能力可表明肿瘤对这些药物的潜在易感性。
