OncoTargets and Therapy (Nov 2019)
Recombinant Viral Capsid Protein L2 (rVL2) of HPV 16 Suppresses Cell Proliferation and Glucose Metabolism via ITGB7/C/EBPβ Signaling Pathway in Cervical Cancer Cell Lines
Abstract
Zhihong Chai,1,* Yufei Yang,2,3,* ZhongYi Gu,4,* Xianli Cai,1 Wenwei Ye,1 Lin Kong,1 Xiaoxiao Qiu,1 Lingxiao Ying,1 Ziliang Wang,2,3 Linyou Wang1 1Department of Gynecology and Department of Radiology, Taizhou Municipal Hospital Affiliated to Taizhou University School of Medicine, Taizhou 318000, People’s Republic of China; 2Department of Obstetrics and Gynecology, Xihua Hospital Affiliated to Shanghai Jiaotong University School Medicine, Shanghai 200092, People’s Republic of China; 3Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 4Department of Nephrology, Children’s Hospital of Fudan University, Shanghai 201102, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ziliang WangDepartment of Obstetrics and Gynecology, Xihua Hospital Affiliated to Shanghai Jiaotong University School Medicine, 1665 Kongjiang Road, Shanghai 200092, People’s Republic of ChinaEmail [email protected] WangDepartment of Radiology, Taizhou Municipal Hospital, 381 East Zhongshan Road, Taizhou 318000, People’s Republic of ChinaEmail [email protected]: Capsid protein L2 is the minor capsid protein of human papillomavirus 16 (HPV16). Although L2-based vaccines were developed, the therapeutic effect of recombinant viral capsid protein L2 (rVL2) was still to be illustrated.Methods: We used glucose uptake and lactate production assay to verify the inhibitory effect of rVL2 on the glucose metabolism in cervical cancer cells. Secondly, we performed gene-chip assay, RT-PCR, and Western blot to determine the role of ITGB7/C/EBPβ signaling pathway in rVL2-mediated glucose metabolism in vitro. Finally, we used an animal model to verify the function of rVL2 in cervical cancer.Results: We found that rVL2 reduced glucose uptake and lactate production levels in cervical cancer cells, which caused the inhibition of cell proliferation. rVL2 decreased the expression levels of key metabolic enzymes, including GLUT1, LDHA, and ALDOA, to affect cell metabolism in cervical cancer cells by inhibiting ITGB7/C/EBPβ signaling pathway in vitro and in vivo.Conclusion: These results demonstrated the vital role of rVL2 in the glycolysis-induced cell growth and proliferation via suppressing ITGB7/C/EBPβ signaling axis.Keywords: recombinant viral capsid protein L2, rVL2, C/EBPβ, glucose metabolism, cervical cancer
