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姜黄素与多西他赛联合作用于PI3K/AKT/mTOR通路以诱导食管鳞状细胞癌自噬和凋亡的联合效应

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

作者信息

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

机构信息

Department of Oncology, Zhujiang Hospital, Southern Medical University/The Second School of Clinical Medicine, Southern Medical University Guangzhou, China.

Second Department of Oncology, Guilin Nanxishan Hospital Guangxi, China.

出版信息

Am J Transl Res. 2021 Jan 15;13(1):57-72. eCollection 2021.

Abstract

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.

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. 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.

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.

摘要

背景

多西他赛(DTX)广泛用于治疗多种恶性肿瘤,但有许多不良反应。姜黄素(CUR)对多种肿瘤细胞也有作用,可降低化疗药物的毒性和副作用以及耐药性的发生。然而,CUR与DTX联合治疗食管癌尚未见报道。

方法

用CUR或DTX单独或两者联合处理人食管鳞状细胞癌(ESCC)KYSE150和KYSE510细胞,通过CCK8、凋亡、划痕愈合和迁移实验检测癌细胞活力。采用电子显微镜和蛋白质免疫印迹实验观察抗肿瘤作用。

结果

CUR与DTX联合显著抑制食管癌细胞的活力和迁移(P<0.01),并进一步促进癌细胞凋亡。此外,CUR与DTX联合时可诱导食管癌细胞自噬。DTX与CUR联合可能通过抑制PI3K/AKT/mTOR信号通路诱导凋亡和自噬。化合物3-甲基腺嘌呤(3MA)抑制DTX和CUR(DC)诱导的自噬,与DC联合时进一步加速凋亡并抑制食管癌细胞增殖。

结论

CUR与DTX联合诱导ESCC凋亡和自噬,可能通过PI3K/AKT/mTOR信号通路发挥作用。自噬抑制剂、CUR与DTX联合可能成为食管癌的一种新治疗策略。

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