Kumari Seema, Badana Anil Kumar, Mohan G Murali, Shailender Naik G, Malla RamaRao
Cancer Biology Lab, Department of Biochemistry, GITAM Institute of Science, GITAM University, Visakhapatnam, India.
Cancer Biology Lab, Department of Biochemistry, GITAM Institute of Science, GITAM University, Visakhapatnam, India.
Biomed Pharmacother. 2017 Jul;91:436-445. doi: 10.1016/j.biopha.2017.04.027. Epub 2017 May 2.
Breast cancer is one of the most frequently diagnosed cancer in woman. Triple-negative breast cancer (TNBC) is most aggressive form of breast cancer. There is a growing interest in the use of natural products in combinational chemotherapy to improve the effectiveness in combating proliferation of cancer cells. Here, we hypothesized that coralyne in combination with paclitaxel may exhibit synergistic effect on inhibition of proliferation, migration and induction of apoptosis in MCF-7 and MDA-MB-231 breast cancer cell lines. MTT and BrdU incorporation assays were performed to study the effect of drugs alone and in combination on cell cytotoxicity and proliferation of the breast cancer cell lines, respectively. Adhesion and wound healing assays were performed to study the cell and extracellular matrix interactions. In addition, expression of proliferation marker ki-67 and apoptotic markers Bax and Bcl-2 was determined to study the effect of coralyne in combination with paclitaxel by reverse transcriptase PCR and confirmed by Western blot. The results indicated the synergism between coralyne and paclitaxel on proliferation and migration of breast cancer cell lines. This study also showed that combinational drug treatment decreased the expression of ki-67 and there was an increase in pro apoptotic factor Bax with decreased in expression of anti-apoptotic factor Bcl-2 in breast cancer cell lines with negligible effect on normal breast cell line. Overall, our data described the promising therapeutic potential of coralyne in combination with paclitaxel in treating breast cancer at lower effective dose.
乳腺癌是女性中最常被诊断出的癌症之一。三阴性乳腺癌(TNBC)是乳腺癌中最具侵袭性的类型。人们越来越关注在联合化疗中使用天然产物,以提高对抗癌细胞增殖的有效性。在此,我们假设珊瑚碱与紫杉醇联合使用可能对MCF-7和MDA-MB-231乳腺癌细胞系的增殖抑制、迁移抑制及凋亡诱导具有协同作用。分别进行MTT和BrdU掺入试验,以研究单独用药及联合用药对乳腺癌细胞系细胞毒性和增殖的影响。进行黏附试验和伤口愈合试验,以研究细胞与细胞外基质的相互作用。此外,通过逆转录PCR测定增殖标志物ki-67以及凋亡标志物Bax和Bcl-2的表达,以研究珊瑚碱与紫杉醇联合使用的效果,并通过蛋白质免疫印迹法进行确认。结果表明珊瑚碱与紫杉醇在乳腺癌细胞系的增殖和迁移方面具有协同作用。本研究还表明,联合药物治疗降低了ki-67的表达,并且在乳腺癌细胞系中促凋亡因子Bax增加,抗凋亡因子Bcl-2的表达减少,而对正常乳腺细胞系的影响可忽略不计。总体而言,我们的数据表明珊瑚碱与紫杉醇联合使用在较低有效剂量下治疗乳腺癌具有广阔的治疗潜力。