The inhibitory effects of lobaplatin, or in combination with gemcitabine on triple-negative breast cancer cells in vitro and in vivo

Abstract

Abstract Objectives To study the therapeutic effects of lobaplatin in combination with conventional chemotherapy drugs on triple-negative breast cancer (TNBC) cells. Methods We used the CCK-8 assay, flow cytometry, western blotting, and immunofluorescence staining methods to detect the effects of lobaplatin or in combination with gemcitabine on the survival, apoptosis, and cell cycle progression of TNBC cells. A cell-derived xenograft mouse model was used to verify the antitumor effects of lobaplatin alone or in combination with gemcitabine. Results Lobaplatin significantly inhibited MDA-MB-468 cell growth in vitro, either alone or in combination with gemcitabine. Lobaplatin arrested the cell cycle at the S phase, induced nuclear cell damage, and promoted apoptosis. Also, the percentage of apoptotic cells was greatly increased when lobaplatin was combined with gemcitabine. Cleaved Caspase-3 and Poly (ADP-Ribose) Polymerase-1 (PARP-1) fragments indicated that lobaplatin promoted apoptosis through the classical pathway. Lobaplatin effectively inhibited the growth of tumors in vivo. Compared with the vehicle group (567.6 ± 126.2 mm3), the tumor volume of the lobaplatin group (302.7 ± 131.6 mm3) was significantly reduced (p<0.01). The combination of lobaplatin and gemcitabine (207.7 ± 83.94 mm3) was a little better than lobaplatin alone in the inhibition of the transplanted tumor (p>0.05). Conclusions Lobaplatin alone or in combination with gemcitabine had significant inhibitory effects on MDA-MB-468 cells in vitro. Lobaplatin also significantly inhibited the growth of nude mice xenografts. The synergistic effect between lobaplatin and gemcitabine in vivo was minimal, perhaps due to the low dose of gemcitabine used.