Wang Jie, Wu Hua Jian, Zhou Chao Zhu, Wang Hao
Department of Surgery, Hushan Hospital, Fudan University, Shanghai 200040, P.R. China.
Fudan University Experimental Teaching Center of Basic Medicine, Fudan University School of Medicine, Shanghai 200040, P.R. China.
Exp Ther Med. 2016 Oct;12(4):2169-2176. doi: 10.3892/etm.2016.3574. Epub 2016 Aug 4.
The present study aimed to investigate the effect of sulfated polysaccharide-protein complex (SPPC) on the antitumor effect of doxorubicin (Dox) on MDA-MB-231 breast cancer cells and . MTT and Annexin V/propidium iodide staining assays demonstrated that SPPC selectively sensitized MDA-MB-231 cells to Dox-induced cytotoxicity. The half maximal inhibitory concentration of Dox against MDA-MB-231 cells was decreased from 5.3 to 1.5 µM when it was used concomitantly with 5 µM SPPC. SPPC potentiated Dox-induced apoptosis in breast cancer cells via the mitochondrial apoptosis signaling pathway by activating caspase-3 and caspase-9. Notably, the caspase inhibitor Z-VAD-fmk diminished the effect of SPPC on Dox-mediated apoptosis. Furthermore, combination treatment with SPPC and Dox markedly reduced the growth of breast cancer xenografts in mice. The present study demonstrated that SPPC was able to enhance the antitumor effect of Dox on breast cancer cells, thus suggesting that SPCC may be used to reduce the cumulative dose of Dox and its associated toxicities in the chemotherapy of breast cancer and other types of cancer.
本研究旨在探讨硫酸化多糖 - 蛋白质复合物（SPPC）对阿霉素（Dox）对MDA - MB - 231乳腺癌细胞抗肿瘤作用的影响。MTT和膜联蛋白V/碘化丙啶染色试验表明，SPPC可选择性地使MDA - MB - 231细胞对Dox诱导的细胞毒性敏感。当Dox与5 μM SPPC联合使用时，其对MDA - MB - 231细胞的半数最大抑制浓度从5.3 μM降至1.5 μM。SPPC通过激活半胱天冬酶 - 3和半胱天冬酶 - 9，经由线粒体凋亡信号通路增强Dox诱导的乳腺癌细胞凋亡。值得注意的是，半胱天冬酶抑制剂Z - VAD - fmk减弱了SPPC对Dox介导凋亡的作用。此外，SPPC与Dox联合治疗显著降低了小鼠乳腺癌异种移植瘤的生长。本研究表明，SPPC能够增强Dox对乳腺癌细胞的抗肿瘤作用，因此提示SPCC可用于降低乳腺癌及其他类型癌症化疗中Dox的累积剂量及其相关毒性。
