Capilliposide C Sensitizes Esophageal Squamous Carcinoma Cells to Oxaliplatin by Inducing Apoptosis Through the PI3K/Akt/mTOR Pathway.
Capilliposide C Sensitizes Esophageal Squamous Carcinoma Cells to Oxaliplatin by Inducing Apoptosis Through the PI3K/Akt/mTOR Pathway.
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DOI：
10.12659/msm.901183
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发表时间：
2017-05-02
期刊：
影响因子：
--
通讯作者：
Zhang N
中科院分区：
文献类型：
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作者：
Shen Z;Xu L;Li J;Zhang N
虽然以铂类药物为基础的化疗是治疗食管癌最有效的策略，但其毒性和耐药性限制了化疗的给药和应用。毛脂苷C （Capilliposide C, CPS-C）是从中草药Lysimachia capillipes Hemsl中分离得到的一种抗癌药物。然而，CPS-C对食管癌的作用尚不清楚。本研究旨在评价CPS-C对提高奥沙利铂治疗食管鳞癌的化疗增敏作用，并探讨其作用机制。人食管鳞状细胞癌（ESCC）采用TE-1和TE-2。在异种移植物模型中进行了几种体外和体内分析，包括MTT，膜联蛋白V/PI， Western blot， TUNEL和免疫组织化学。CPS-C显著增强奥沙利铂对ESCC细胞的增殖抑制和凋亡作用。与单用奥沙利铂相比，奥沙利铂联合CPS-C可显著降低PI3K、phospho-Akt、phospho-mTOR、Bcl-2、Bcl-XL的表达，显著升高Bax、caspase-3的表达。此外，在ESCC异种移植模型中，CPS-C显著增强奥沙利铂的抗癌作用和细胞凋亡。结果表明，CPS-C在体外和体内通过调节PI3K/Akt/mTOR通路，增强奥沙利铂对ESCC的抗增殖和凋亡作用。
Although platinum-based chemotherapy is the most effective strategy for esophageal cancer, toxicity and drug resistance limit the dose administration and the application of chemotherapy. Capilliposide C (CPS-C) is isolated from the Chinese herb Lysimachia capillipes Hemsl and is approved to be effective against carcinomas. However, the activity of CPS-C against esophageal cancer remains unclear. The present study was conducted to assess the chemosensitizing effects of CPS-C for enhancing the therapeutic efficacy of oxaliplatin in esophageal squamous carcinoma cells and explore the underlying mechanism. Human esophageal squamous cell carcinoma (ESCC) TE-1 and TE-2 were used. Several in vitro and in vivo analyses were carried out, including MTT, Annexin V/PI, Western blot, and TUNEL and immunohistochemistry in a xenograft model. CPS-C significantly enhanced the proliferative inhibition and apoptotic effect of oxaliplatin in ESCC cells. Oxaliplatin combined with CPS-C decreased the expressions of PI3K, phospho-Akt, phospho-mTOR, Bcl-2, and Bcl-XL, and increased the expression of Bax and caspase-3 significantly compared to oxaliplatin-only treatment. Furthermore, in the ESCC xenograft model, CPS-C significantly enhanced the anti-cancer effects and apoptosis of oxaliplatin. The results indicated that CPS-C enhanced the anti-proliferative and apoptotic effect of oxaliplatin by modulating the PI3K/Akt/mTOR pathway on ESCC in vitro and in vivo.