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Ilex hainanensis Merr targets ITGAV to suppress the proliferation and metastasis of osteosarcoma cells

Authors Pei Y, Zhang YY, Zheng K, Shang GN, Wang YM, Wang W, Qiu ED, Li SL, Liu F, Zhang XJ

Received 16 February 2019

Accepted for publication 27 April 2019

Published 7 June 2019 Volume 2019:12 Pages 4499—4507

DOI https://doi.org/10.2147/OTT.S205688

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Aruna Narula

Peer reviewer comments 2

Editor who approved publication: Dr Tohru Yamada


Yi Pei,1 YueYan Zhang,2 Ke Zheng,1 GuanNing Shang,1 YuMing Wang,1 Wei Wang,1 EnDuo Qiu,1 ShengLong Li,1 Fei Liu,1 XiaoJing Zhang1

1Department of Bone and Soft Tissue Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, People’s Republic of China; 2Clinical Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, People’s Republic of China

Background: Osteosarcoma (OS) is the most common primary malignant bone tumor. Hence, there is an urgent need to identify effective and safe therapeutic agents against OS. It has been reported that Ilex hainanensis Merr (IME) possesses antitumor properties. Integrin subunit alpha V (ITGAV) is important for the diagnosis, treatment, and prognosis of tumors.
Purpose: The objective of this study was to whether IME can play a role in the treatment of osteosarcoma by regulating ITGAV.
Methods: Western blot and real-time PCR were used to detect the expression of ITGAV in non-tumorous tissues, osteosarcoma tissues, and metastatic tumors. The expression of ITGAV in MG63, U2OS, and hFOB1. A total of 19 cells was determined through Western blotting and real-time PCR. The expression of ITGAV in OS cells treated with different concentrations of DDP was determined through Western blotting. Agter transfecting with control or si-ITGAV, and subsequently treated with control or 5 μmol/L DDP, MTT assay and transwell assay were used to detect the proliferaion and migration of cells. Western blot was used to detect the expression of ITGAV in cells treated with different concentrations of IME and MTT assay and transwell assay were used to detect the proliferaion and migration of cells. MG63 and U2OS cells were treated with control, 5 μmol/L DDP, 25 μmol/L IME, or 5 μmol/L DDP combined with 25 μmol/L IME, the expression of ITGAV was determined through Western blotting and real-time PCR. MTT assay and transwell assay were used to detect the proliferation and migration of cells. Inhibitory effect of IME on lung metastasis of osteosarcoma in vivo.
Results: ITGAV was highly expressed in tumors, with the highest expression found in metastatic tumors and higher in OS cells. A low concentration of DDP (5 μmol/L) inhibited the expression of ITGAV. However, ITGAV may be related to the development of resistance to DDP. Silencing of ITGAV downregulates the proliferation and migration of OS cells as the effect of low-concentration DDP (5 μmol/L). IME inhibited the proliferation and migration of MG63 and U2OS cells in a concentration-dependent manner and decreased the expression of ITGAV. MTT and Transwell assays showed that 25 μmol/L IME and 5 μmol/L DDP exhibited similar inhibitory effects on the proliferation and migration of OS cells. The combination of IME with DDP resulted in the amplification of these inhibitory effects. Both DDP and IME downregulated the expression of ITGAV, and the inhibition of ITGAV was amplified by the combination of IME with DDP. In-vivo studies have shown that IME and DDP, independently or in combination, may significantly inhibit the metastasis of OS to the lungs.
Conclusion: IME may reduce the resistance of OS cells to DDP to some extent.

Keywords: Ilex hainanensis Merr, osteosarcoma, integrin subunit alpha V, cisplatin

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