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

Zhang,Yuyan; Huang,Jiusui; Huang,Yapeng; Zhang,Shike; Wu,Weizhou; Long,Hui; Duan,Xiaolu; Lai,Yongchang; Wu,Wenqi

doi:10.3892/mmr.2020.11678

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

Authors:
- Yuyan Zhang
- Jiusui Huang
- Yapeng Huang
- Shike Zhang
- Weizhou Wu
- Hui Long
- Xiaolu Duan
- Yongchang Lai
- Wenqi Wu
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Affiliations: Department of Pharmacy, Guangzhou Institute of Dermatology, Guangzhou, Guangdong 510095, P.R. China, Department of Urology, Minimally Invasive Surgery Centre, Guangzhou Urology Research Institute, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510230, P.R. China, Department of Urology, The Eighth Affiliated Hospital, Sun Yat‑sen University, Shenzhen, Guangdong 518033, P.R. China
Published online on: November 10, 2020 https://doi.org/10.3892/mmr.2020.11678
Article Number: 40
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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