Deguelin induces apoptosis in colorectal cancer cells by activating the p38 MAPK pathway
Deguelin induces apoptosis in colorectal cancer cells by activating the p38 MAPK pathway
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Deguelin 通过激活 p38 MAPK 通路诱导结直肠癌细胞凋亡
DOI：
10.2147/cmar.s169476
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Ding, Kefeng
中科院分区：
文献类型：
--
作者：
Chen, Liubo;Jiang, Kai;Ding, Kefeng
目的从豆科植物蚕豆中提取的类鱼素Deguelin对多种人类癌症具有抗肿瘤作用。由于去圭林对结直肠癌（CRC）的研究有限，本研究旨在研究去圭林的抗肿瘤作用，并探讨其在结直肠癌中的潜在机制。材料与方法用细胞计数试剂盒-8 （CCK-8）法测定结直肠癌细胞株的细胞活力，用流式细胞术和Western blot检测膜联蛋白v-碘化丙啶染色法检测细胞凋亡。在异种肿瘤移植模型中进一步评价去桂林的抗肿瘤作用。此外，我们使用p38 MAPK的特异性抑制剂SB203580来证实p38 MAPK通路参与deguelin诱导的细胞凋亡。结果去桂林显著抑制结直肠癌细胞株（SW620和RKO）细胞增殖，诱导细胞凋亡，并呈时间依赖性和剂量依赖性。Western blot分析还显示，去胶蛋白处理CRC细胞株后，促凋亡蛋白（cleaved caspase 3和cleaved PARP）表达上调，而抗凋亡蛋白（Bcl-2和survivin）表达下调。此外，口服去桂林可显著抑制皮下移植小鼠模型的肿瘤生长和诱导细胞凋亡，且无明显毒性。此外，Western blot结果显示，去胶蛋白诱导的CRC细胞凋亡可能受p38 MAPK通路的调控，抑制p38 MAPK可减轻去胶蛋白诱导的CRC细胞增殖抑制和凋亡。综上所述，去桂林通过激活p38 MAPK通路诱导细胞凋亡，从而抑制结直肠癌细胞的生长。
Objectives Deguelin, a rotenoid extracted from Mundulea sericea (Leguminosae), exhibits antitumor effects on several types of human cancers. Due to the limited studies of deguelin on colorectal cancer (CRC), the present study was designed to investigate the antitumor effect of deguelin and to explore the underlying mechanism in CRC. Materials and methods Cell viability was assessed by the cell counting kit-8 (CCK-8) assay, and cell apoptosis was determined by the annexin v-propidium iodide staining using flow cytometry and Western blot in CRC cell lines after incubation with deguelin. The antitumor effect of deguelin was further evaluated in tumor xenograft models. Moreover, SB203580, a specific inhibitor of p38 MAPK, was used to confirm the involvement of p38 MAPK pathway in deguelin-induced apoptosis. Results Deguelin significantly inhibited cell proliferation and induced apoptosis in CRC cell lines (SW620 and RKO) in a time-dependent and dose-dependent manner. Western blot analysis also showed that the expression of proapoptotic proteins (cleaved caspase 3 and cleaved PARP) was upregulated, while that of antiapoptotic proteins (Bcl-2 and survivin) was downregulated after deguelin treatment in CRC cell lines. Moreover, oral administration of deguelin significantly suppressed tumor growth and induced apoptosis in subcutaneous xenograft mouse models without obvious toxicity. Additionally, Western blot revealed that deguelin-induced apoptosis might be regulated by the p38 MAPK pathway and inhibition of p38 MAPK could attenuate deguelin-induced proliferative inhibition and apoptosis in CRC cells. Conclusion Collectively, these results demonstrated that deguelin inhibited CRC cell growth by inducing apoptosis via activation of p38 MAPK pathway.