Department of Biology, School of Natural Sciences, University of Tabriz, Tabriz P.O. Box 5166616471, Iran.
Department of Medical Laboratory Technology, Erbil Health and Medical Technical College, Erbil Polytechnic University, Erbil 44001, Iraq.
Molecules. 2022 May 3;27(9):2917. doi: 10.3390/molecules27092917.
Triple Negative Breast Cancer (TNBC) is the aggressive and lethal type of breast malignancy that develops resistance to current therapies. Combination therapy has proven to be an effective strategy on TNBC. We aimed to study whether the nano-formulation of polyphenolic curcumin (Gemini-Cur) would affect the cisplatin-induced toxicity in MDA-MB-231 breast cancer cells. MDA-MB-231 cells were treated with Gemini-Cur, cisplatin and combination of Gemini-Cur/Cisplatin in a time- and dose-dependent manner. Cell viability was studied by using MTT, fluorescence microscopy and cell cycle assays. The mode of death was also determined by Hoechst staining and annexin V-FITC. Real-time PCR and western blotting were employed to detect the expression of BAX and BCL-2 genes. Our data demonstrated that Gemini-Cur significantly sensitizes cancer cells to cisplatin (combination index ≤ 1) and decreases IC50 values in comparison with Gemini-cur or cisplatin. Further studies confirmed that Gemini-Cur/Cisplatin suppresses cancer cell growth through induction of apoptosis (p < 0.001). In conclusion, the data confirm the synergistic effect of polyphenolic curcumin on cisplatin toxicity and provide attractive strategy to attain its apoptotic effect on TNBC.
三阴性乳腺癌(TNBC)是一种侵袭性和致命性的乳腺癌,对目前的治疗方法产生耐药性。联合治疗已被证明是治疗 TNBC 的有效策略。我们旨在研究多酚姜黄素(Gemini-Cur)的纳米制剂是否会影响顺铂诱导的 MDA-MB-231 乳腺癌细胞毒性。MDA-MB-231 细胞以时间和剂量依赖性方式用 Gemini-Cur、顺铂和 Gemini-Cur/Cisplatin 联合处理。通过 MTT、荧光显微镜和细胞周期分析研究细胞活力。通过 Hoechst 染色和 Annexin V-FITC 确定死亡方式。Real-time PCR 和 Western blotting 用于检测 BAX 和 BCL-2 基因的表达。我们的数据表明,与单独使用 Gemini-cur 或顺铂相比,Gemini-Cur 显著增强了癌细胞对顺铂的敏感性(组合指数≤1)并降低了 IC50 值。进一步的研究证实,Gemini-Cur/Cisplatin 通过诱导细胞凋亡抑制癌细胞生长(p < 0.001)。总之,这些数据证实了多酚姜黄素对顺铂毒性的协同作用,并为实现其对 TNBC 的凋亡作用提供了有吸引力的策略。