Tanshinone I and simvastatin inhibit melanoma tumour cell growth by regulating poly (ADP ribose) polymerase 1 expression

Melanoma is one of the most aggressive forms of skin tumour with poor prognosis; no effective therapy has been established for melanoma at the metastatic stage. The present study aimed to investigate the role of poly (ADP ribose) polymerase (PARP) inhibitors (PARPis) and PARP1 expression in melanoma progression. In addition, whether high PARP1 expression was associated with poor overall survival in melanoma, and whether a combination effect existed between PARPis and other anti-tumour compounds (e.g., sunitinib) was analysed. The PARP1 expression was detected using western blot analysis and the proliferation of cells was detected with a colony formation assay. In addition, cell viability assays and xenograft tumor experiments were conducted. The results of the present study demonstrated that sunitinib reduced PARP1 expression and proliferation of melanoma cells. Notably, one of the PARPis, veliparib, reversed the inhibitory effect of sunitinib on PARP1 expression and proliferation, indicating that inhibition of PARP1 enzyme activity by PARPi may be different from the inhibition of PARP1 expression in melanoma cell biological function. To further confirm the relationship between PARP1 expression and tumour cell proliferation, seven compounds, including common approved drugs and natural Chinese medicine monomers, were screened, and the results demonstrated that simvastatin and tanshinone I exerted an inhibitory effect on PARP1 expression and melanoma cell proliferation, and their combination was more effective than simvastatin alone in vivo. The results indicated that simvastatin and tanshinone I inhibited melanoma and renal tumour cells by regulating PARP1 expression, and in addition to the enzyme activity of PARP1, the expression of PARP1 protein may serve a role in tumour progression.

Automated summary

This study explored the impact of PARP inhibitors and PARP1 expression on melanoma progression, revealing that sunitinib reduced PARP1 expression and proliferation of melanoma cells, while the PARPi veliparib reversed this effect. Additionally, simvastatin and tanshinone I were found to inhibit melanoma cell proliferation by regulating PARP1 expression, with their combination showing synergistic effects in vivo. These results highlight the potential role of PARP1 expression in tumour progression and suggest that targeting PARP1 may offer a novel therapeutic approach for melanoma.