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Propranolol enhanced the anti-tumor effect of sunitinib by inhibiting proliferation and inducing G0/G1/S phase arrest in malignant melanoma.

ABSTRACT: Both sunitinib, a multi-target tyrosine kinase inhibitor (TKI) and propranolol, a non-selective ?-blocker, have proven therapeutic effects on malignant melanoma (MM). This study reports a synergistic effect of propranolol and sunitinib upon A375, P8 MM cell lines and mice xenografts. Cell viability assays detected a significant decrease of sunitinib IC50 in combination with propranolol, which was confirmed by a colony formation assay. Western blot showed that propranolol and sunitinib combination significantly down-regulated phospho-Rb, phospho-ERK, Cyclin D1, and Cyclin E, but had no effect on Bax, Bcl-2, or cleaved PARP expression. The average tumor size of propranolol and low-dose sunitinib (Sun L) combination treated mice was reduced and similar to high-dose sunitinib treated A375 xenografts. The Ki67 index was significantly reduced in propranolol and Sun L combination treated group compared with single Sun L treated group. This synergistic effect between propranolol and sunitinib to inhibit MM proliferation was through suppressing ERK/Cyclin D1/Rb/Cyclin E pathways and inducing G0/G1/S phase arrest, rather than by inducing tumor cell apoptosis.

SUBMITTER: Kuang X

PROVIDER: S-EPMC5787512 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Propranolol enhanced the anti-tumor effect of sunitinib by inhibiting proliferation and inducing G0/G1/S phase arrest in malignant melanoma.

Kuang Xinwei X Qi Min M Peng Cong C Zhou Chengfang C Su Juan J Zeng Weiqi W Liu Hong H Zhang Jianglin J Chen Mingliang M Shen Minxue M Xie Xiaoyun X Li Fangfang F Zhao Shuang S Li Qingling Q Luo Zhongling Z Chen Junchen J Tao Juan J He Yijing Y Chen Xiang X

Oncotarget 20171125 1

Both sunitinib, a multi-target tyrosine kinase inhibitor (TKI) and propranolol, a non-selective β-blocker, have proven therapeutic effects on malignant melanoma (MM). This study reports a synergistic effect of propranolol and sunitinib upon A375, P8 MM cell lines and mice xenografts. Cell viability assays detected a significant decrease of sunitinib IC50 in combination with propranolol, which was confirmed by a colony formation assay. Western blot showed that propranolol and sunitinib combinatio ...[more]

PMID: 29416656

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Dataset Information

Propranolol enhanced the anti-tumor effect of sunitinib by inhibiting proliferation and inducing G0/G1/S phase arrest in malignant melanoma.

Publications

Propranolol enhanced the anti-tumor effect of sunitinib by inhibiting proliferation and inducing G0/G1/S phase arrest in malignant melanoma.

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