Curcumin induces apoptosis and autophagy inhuman renal cell carcinoma cells via Akt/mTOR suppression.

Curcumin induces apoptosis and autophagy inhuman renal cell carcinoma cells via Akt/mTOR suppression.
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DOI:
10.1080/21655979.2021.1960765
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发表时间:
2021-12
期刊:
影响因子:
4.9
通讯作者:
Li Z
Li Z
中科院分区:
生物学2区
文献类型:
--
作者:
Gong X;Jiang L;Li W;Liang Q;Li Z

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肾细胞癌(Renal cell carcinoma,RCC)是一种侵袭性很强的恶性肿瘤,其发病率逐年上升,给社会和经济带来巨大负担。姜黄素是一种广泛应用于抗炎、抗病毒和抗癌的中药,因此可用于肾细胞癌的治疗。本研究评价了姜黄素、姜黄素+3-MA、姜黄素+ CQ或姜黄素+ Z-VAD对肾癌细胞的体内外治疗作用,并探讨了其抑制肿瘤细胞增殖的机制。该研究使用ACHN肿瘤细胞和C57 BL/6裸鼠进行结果验证。MTT法检测细胞增殖,Annexin V-FITC/PI试剂盒和流式细胞仪检测细胞凋亡。采用酶联免疫吸附试验(ELISA)检测各组细胞因子IL-6、IL-8和TNF-α的表达。Western blot和免疫荧光检测AKT/mTOR和自噬蛋白的表达。结果表明,与对照相比,用姜黄素单独或与各种组合处理ACHN肿瘤细胞后,细胞活力显著抑制。姜黄素处理后细胞凋亡明显增加,但姜黄素+ 3-MA处理后细胞凋亡明显逆转。同样,姜黄素治疗后,AKT/mTOR蛋白表达显著降低,而自噬相关蛋白显著升高。姜黄素治疗后,肿瘤的大小、重量和体积也得到了显著抑制。总之,研究表明姜黄素通过抑制AKT/mTOR通路抑制ACHN细胞活力,诱导凋亡和自噬。姜黄素靶向AKT/mTOR通路可能是肾细胞癌的有效治疗选择。
Renal cell carcinoma (RCC) is a highly aggressive cancer leading to high economic and social burden, and has increasing annual cases. Curcumin is a traditional Chinese medicine widely used as anti-inflammatory, anti-viral and anti-cancer agent, thus can be applicable in RCC therapy. The work assessed the effects of RCC treatment with Curcumin, Curcumin+3-MA, Curcumin+ CQ or curcumin+ Z-VAD in vitro and in vivo, and the mechanisms involved in inhibition of tumor cells proliferation. The study used ACHN tumor cells and C57BL/6 nude mice for results validation. Cell proliferation was determined through MTT assays while apoptosis was investigated using Annexin V-FITC/PI kit and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to detect IL-6, IL-8, and TNF-α cytokines expressions. AKT/mTOR and autophagy proteins expressions were investigated through western blot and immunofluorescence. The results indicated significantly inhibited cell viability following ACHN tumor cells treatments with curcumin alone, or with the various combinations, as compared to the control. Apoptosis was significantly increased following curcumin treatment, but was significantly reversed after treatment with curcumin+ 3-MA. Likewise, AKT/mTOR proteins expression were significantly reduced while the autophagy-related proteins were significantly elevated following curcumin treatment. The tumor size, weight and volumes were also significantly suppressed following treatment with curcumin. In conclusion, the investigation demonstrated that curcumin suppressed ACHN cell viability, induced apoptosis and autophagy, through the suppression of AKT/mTOR pathway. Use of curcumin to target AKT/mTOR pathway could be an effective treatment alternative for renal cell carcinoma.
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