Combination effect of curcumin with docetaxel on the PI3K/AKT/mTOR pathway to induce autophagy and apoptosis in esophageal squamous cell carcinoma

姜黄素联合多西他赛对PI3K/AKT/mTOR通路诱导食管鳞状细胞癌自噬与凋亡的影响

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作者:Lian Deng, Xiaoran Wu, Xiongjie Zhu, Zhongjian Yu, Zhile Liu, Jinting Wang, Yanfang Zheng

Background

Docetaxel (DTX) is widely used to treat many malignant tumors but has many adverse effects. Curcumin (CUR) also has effects on a variety of tumor cells and can reduce the toxicity and side effects of chemotherapy drugs and the occurrence of drug resistance. However, the combination of CUR and DTX for treating esophageal cancer has not been reported.

Conclusion

CUR combined with DTX induced apoptosis and autophagy of ESCC and probably worked through the PI3K/AKT/mTOR signaling pathway. The combination of the autophagy inhibitor, CUR and DTX may become a new treatment strategy for esophageal cancer.

Methods

Human esophageal squamous cell carcinoma (ESCC) KYSE150 and KYSE510 cells were treated with CUR or DTX alone or both drugs and cancer cell viability was detected by CCK8, apoptosis, scratch-healing and migration assays. Electron microscopy and Western blots were used. In vivo experiments were used observe anti-tumor effects.

Results

CUR combined with DTX significantly inhibited the viability and migration of esophageal cancer cells (P<0.01) and further promoted the apoptosis of cancer cells. In addition, CUR induced autophagy in esophageal cancer cells when combined with DTX. DTX combined with CUR may induce apoptosis and autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway. The compound 3-methyladenine (3MA) inhibited the autophagy induced by DTX and CUR (DC), further accelerated apoptosis and inhibited the proliferation of esophageal cancer cells when combined with DC.

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