Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, (U.P.), India.
Department of Chemistry, North-Eastern Hill University, Shillong 793022, (Meghalaya), India.
Life Sci. 2022 Nov 1;308:120937. doi: 10.1016/j.lfs.2022.120937. Epub 2022 Sep 9.
Currently, breast cancer is one of the most frequently diagnosed and the second leading cause of cancer related deaths in women worldwide. Our present study aimed to investigate the major mechanistic effects of micelles (TSD-30-F, TSD-34-F) on breast cancer cells as well as their antitumor efficacy in in vivo DL bearing BALB/c mice.
Apoptotic death by micelles was investigated by mitochondrial aggregation, membrane potential and DNA fragmentation assay in MCF-7 and MDA-MB-231 cells. Molecular mode of action of micelles were determined by RT-PCR and western blot analysis, drug-ligand interaction was analyzed by in silico methods, while, in vivo antitumor activity was investigated by Kaplen-Meier survival curve, T/C value, body weight and belly size of BALB/c mice.
TSD-30-F and TSD-34-F micelles displayed significant apoptotic induction. At molecular level, TSD-30 and TSD-34 micelles showed up-regulation of p53, Bax, Bak, Caspase-3 and down-regulation of Bcl-2 genes as well as proteins in tested breast cancer cells. In silico analysis revealed that TSD-30 and TSD-34 showed efficient binding affinity with p53, Caspase-3, Bax and Bcl-2 proteins. Significant in vivo antitumor efficacy was exhibited by the micelles formulations by increasing life span with reduced bodyweight and belly size growth pattern in BALB/c mice compared to DTX-F micelles.
Our results suggest that triphenyltin (IV) micelles could be a very promising therapeutic candidate for treatment of breast cancer patients and occupy a new place in targeted breast cancer therapeutic.
目前，乳腺癌是全球女性最常见的诊断和癌症相关死亡的第二大原因。本研究旨在探讨胶束（TSD-30-F、TSD-34-F）对乳腺癌细胞的主要作用机制及其在体内携带 DL 的 BALB/c 小鼠中的抗肿瘤功效。
通过 MCF-7 和 MDA-MB-231 细胞中线粒体聚集、膜电位和 DNA 片段化测定研究胶束诱导的细胞凋亡。通过 RT-PCR 和 Western blot 分析确定胶束的分子作用模式，通过计算方法分析药物-配体相互作用，通过 Kaplen-Meier 生存曲线、T/C 值、BALB/c 小鼠体重和腹部大小研究体内抗肿瘤活性。
TSD-30-F 和 TSD-34-F 胶束显示出显著的凋亡诱导作用。在分子水平上，TSD-30 和 TSD-34 胶束在测试的乳腺癌细胞中上调了 p53、Bax、Bak、Caspase-3 基因，并下调了 Bcl-2 基因和蛋白。计算分析表明，TSD-30 和 TSD-34 与 p53、Caspase-3、Bax 和 Bcl-2 蛋白具有有效的结合亲和力。与 DTX-F 胶束相比，胶束制剂在 BALB/c 小鼠中表现出显著的抗肿瘤功效，增加了寿命，降低了体重和腹部大小的生长模式。
我们的结果表明，三苯基锡（IV）胶束可能是治疗乳腺癌患者的极有前途的治疗候选物，并在靶向乳腺癌治疗中占据新的地位。
