Oleic Acid Promotes Cervical Cancer Cell Proliferation And Migration Through CD36 Associated Molecular Mechanism

Objective: To study the effect high oleic acid diet on the growth and metastasis of cervical cancer and the role of CD36 in the process.Methods: Part 1: In vivo,nude mice were divided into normal diet group,high-oleic-acidt diet group(containing 45%(kal%)olive oil).Cervical cancer cell line Hela cells were injected subcutaneously or via tail vein to establish tumor growth model or metastasis model,while growth curve was recorded and liver metastasis were observed grossly or detected by HE staining.In vitro,Hela cells were treated with different concentrations of oleic acids and cell proliferation and viability were assayed by using the CCK-8 reagent and plate colony formation assay,while cell cycle was measured by flow cytometry.And cell migration or invasion was detected by Transwell assay;Part 2: The expression of PCNA and CD36 in tumor tissues were detected by histochemistry.And CD36 mRNA levels in tumor tissue and cells were detected by real-time quantitative PCR.CD36 overexpression cell line was constructed to studythe effect of CD36 overexpression on cell proliferaion,cell cycle and migration in vitro.And the effect of CD36 overexpression on tumor growth was observed in vivo.Furthermore,CD36 knockdown by siRNA lentivirus were applied to observe the effect of CD36 inhibition on the proliferation,migration and other changes in vitro.Results: Part 1: In vivo,we found that the volumes and weights of subcutaneous tumors in high-oleic-acid diet group were increased more than 10 times than those in the normal diet group(P<0.05),and 4 in 10 mice of the high-oleic-acid diet group had liver metastasis observed by nude eyes,while in the normal diet group it was only 1 in 11 mice(P<0.05).And the area and number of metastases in the high-oleic-acid diet group were significantly larger than those in the normal diet group(P<0.05).In vitro,compared to the control group,the proliferation,migration,invasion,S phase ratio of the cell cycle and the number of colonies formed in the oleic acid treated group were all significantly increased(P <0.05),and the cell proliferation,migration and invasion were increased by the oleic acid in a dose-dependent manner.Part II: Immunohistochemistry and qPCR all suggested that oleic acid could stimulate CD36 expression(P<0.05).After overexpression of CD36 in cell lines,cell proliferation,S phase percentages of cell cycle,and migration were significantly increased(P<0.05),tumor growth curve,volume,and weight of nude mice of the CD36 overexpression group were also significantly increased(P<0.05).However,after CD36 knockdown,the cell proliferation or migration were decreased significantly as expected(P<0.05).Conclusion: High oleic acid diet can promote the growth and metastasis of cervical cancer in vitro or in vivo and stimulate CD36 expression.AndCD36 overexpression can promote the development of cervical cancer while inhibition of CD36 can alleviate the high oleic acid-promoted tumor cell proliferation and migration ability.We concluded that oleic acid can promote cervical cancer cells' proliferation and migration through CD36 associated molecular mechanism...