蛇床子素通过 PTEN/AKT 通路使 CD133 阳性肝癌细胞对顺铂重新敏感。
Osthole resensitizes CD133 hepatocellular carcinoma cells to cisplatin treatment via PTEN/AKT pathway.
机构信息
Department of Hepato-Biliary-Pancreatic Surgery, First Hospital Jilin University, Changchun 130021, Jilin Province, China.
Department of Colorectal and Anal Surgery, First Hospital Jilin University, Changchun 130021, Jilin Province,130021, China.
出版信息
Aging (Albany NY). 2020 Jul 16;12(14):14406-14417. doi: 10.18632/aging.103484.
The population of CD133 positive cancer cells has been reported to be responsible for drug resistance of hepatocellular carcinoma (HCC). However, the potential molecular mechanism by which CD133 HCC cells develop drug resistance is still unclear. In this study, we found that CD133 HepG2 and Huh7 cells were resistant to cisplatin treatment, compared to the CD133 HepG2 and Huh7 cells. However, treatment with osthole, a natural coumarin isolated from umbelliferae plant monomers, was found to resensitize CD133 HepG2 and Huh7 cells to cisplatin treatment. In the mechanism research, we found that treatment with osthole increased the expression of PTEN. As a result, osthole inhibited the phosphorylation of AKT and Bad to decrease the amount of free Bcl-2 in CD133 HepG2 and Huh7 cells. Finally, cisplatin-induced mitochondrial apoptosis was expanded. In conclusion, combination treatment with osthole can resensitize CD133 HCC cells to cisplatin treatment via the PTEN/AKT pathway.
CD133 阳性癌细胞的群体已被报道为导致肝癌（HCC）耐药的原因。然而，CD133 HCC 细胞产生耐药性的潜在分子机制仍不清楚。在这项研究中，我们发现与 CD133 HepG2 和 Huh7 细胞相比，CD133 HepG2 和 Huh7 细胞对顺铂治疗具有耐药性。然而，用蛇床子素（一种从伞形科植物单体中分离出来的天然香豆素）治疗发现可以使 CD133 HepG2 和 Huh7 细胞对顺铂治疗重新敏感。在机制研究中，我们发现蛇床子素处理增加了 PTEN 的表达。结果，蛇床子素抑制 AKT 和 Bad 的磷酸化，减少 CD133 HepG2 和 Huh7 细胞中游离 Bcl-2 的量。最后，扩大了顺铂诱导的线粒体凋亡。总之，通过 PTEN/AKT 通路，蛇床子素联合治疗可以使 CD133 HCC 细胞对顺铂治疗重新敏感。
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