Proteasome inhibitor MG132 reverses multidrug resistance of gastric cancer through enhancing apoptosis and inhibiting P-gp
Proteasome inhibitor MG132 reverses multidrug resistance of gastric cancer through enhancing apoptosis and inhibiting P-gp
复制标题
蛋白酶体抑制剂MG132通过增强细胞凋亡和抑制P-gp逆转胃癌多药耐药
DOI：
10.4161/cbt.7.4.5483
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发表时间：
2008-04
影响因子：
3.6
通讯作者：
Zhang, Yafei
中科院分区：
文献类型：
--
作者：
Wu, Kaichun;Xia, Lin;Zhai, Huihong;Li, Xiaohua;Chen, Bei;Luo, Guanhong;Du, Wenqi;Shi, Yongquan;Du, Rui;Fan, Daiming;Zhang, Yafei
摘要多药耐药（MDR）是许多恶性肿瘤有效化疗的主要障碍。尽管人们在开发克服MDR的新药方面做了大量的工作，但到目前为止，仍然没有出现适用于临床的逆转MDR的有效方法。有研究报道蛋白酶体抑制剂可诱导多种肿瘤细胞凋亡。本研究发现，蛋白酶体抑制剂MG 132能有效诱导胃癌细胞株SGC 7901/VCR的凋亡，并能下调抗凋亡基因Bcl-2和MDR 1（P-gp）的表达，从而使胃癌细胞对抗癌药物诱导的凋亡重新敏感。药敏实验结果进一步证明，MG 132可通过促进药物诱导的细胞凋亡和抑制P-gp的表达，有效逆转胃癌细胞的耐药表型。进一步研究蛋白酶体抑制剂在体内的有效性和安全性，可能有助于开发治疗胃癌MDR的新策略。
ABSTRACT Multidrug resistance (MDR) is a major impediment to the effective chemotherapy of many human malignancies. Although much effort has been devoted to develop new drugs for overcoming MDR, until now, still no useful method of reversing MDR, suitable for clinical use, has emerged from this large quantity of work. Some researchers have reported that proteasome inhibitors could induce apoptosis in a variety of cancer cells. In the present study, we found that, in vincristine-resistant human gastric cancer cell line SGC7901/VCR, proteasome inhibitor MG132 was an effective inducer of apoptosis, and also had the capacity of downregulating the expression of anti-apoptotic Bcl-2 and MDR1 (P-gp), by which MG132 resensitized tumor cells to the apoptosis induced by anticancer drugs. Data presented by drug sensitivity assay further demonstrated that MG132 could reverse the resistant phenotype of gastric cancer cells effectively through both enhancing drug-induced apoptosis and inhibiting P-gp. The further study of the effectiveness and safety of proteasome inhibitor in vivo may be helpful for developing a new possible strategy to treat gastric cancer MDR.
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影响因子：
3.3
作者：
P. Richardson;C. Mitsiades
通讯作者：
P. Richardson;C. Mitsiades
影响因子：
3.3
作者：
K. Tobinai
通讯作者：
K. Tobinai
DOI：
10.1111/j.1440-1746.2005.03797.x
发表时间：
2005-03-01
影响因子：
4.1
作者：
Fan, DM;Zhang, XY;Wu, KC
通讯作者：
Wu, KC
影响因子：
3.5
作者：
Wu, HM;Chi, KH;Lin, WW
通讯作者：
Lin, WW
影响因子：
6.5
作者：
Masdehors, P;Omura, S;Delic, J
通讯作者：
Delic, J