Lobaplatin induces apoptosis in T24 and 5637 bladder cancer cells by regulating Bcl-2 and Bax expression and inhibiting the PI3K/Akt signaling pathway.

ABSTRACT:

Background

Lobaplatin (LBP) is a third-generation platinum-based drug that has been approved only in China for the treatment of several cancer types. Nonetheless, its efficacy in treating bladder cancer (BC) is unclear thus far. Through in vitro and in vivo experiments, this study aimed to explore whether LBP has an antitumor effect on T24 and 5637 BC cells and whether the effect is related to B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and regulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway.

Methods

For in vitro experiments, the cell counting kit-8 (CCK-8) method was used to determine how different concentrations of LBP affect the viability of two types of BC cells. A wound healing assay was used to test the inhibitory effect of LBP on the migration of the two cell lines. Annexin V-fluorescein isothiocyanate isomer I (V-FITC)/propidium iodide (PI) staining was used to detect changes in cell apoptosis before and after LBP treatment, and Western blotting was used to detect the expression of apoptosis-related proteins and PI3K/Akt pathway proteins. For in vivo experiments, a cell-derived xenograft (CDX) model was employed, and the weight of nude mice and the tumor size were measured. Immunohistochemistry was used to detect the effect of LBP on the expression of apoptosis-related proteins in tumor xenografts.

Results

In vitro, LBP reduced proliferation (P<0.05), inhibited migration (P<0.05), and induced apoptosis in T24 (31.25%±1.20%, P<0.01) and 5637 (14.3%±2.24%, P<0.05) BC cells, in a dose-dependent manner (P<0.05); increased the expression of proapoptotic proteins, including Bax, caspase-3 and cleaved caspase-3 (P<0.05); and suppressed the expression of antiapoptotic proteins, including Bcl-2, PI3K, Akt and phosphorylated Akt (p-Akt). The in vivo experiment confirmed that LBP can reduce the size of subcutaneous tumors in nude mice (P<0.05), increase the expression levels of Bax and cleaved caspase-3 and lower the expression of Bcl-2 (P<0.05) in bladder tumor tissue.

Conclusions

The results obtained from both experiments suggest that LBP can inhibit the proliferation of T24 and 5637 BC cells, which might be credited to its effects in regulating Bcl-2 and Bax expression and inhibiting the PI3K/Akt pathway.

SUBMITTER: Yu Q 

PROVIDER: S-EPMC10481196 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature