Cancer Management and Research (Apr 2020)
Targeting PIK3CG in Combination with Paclitaxel as a Potential Therapeutic Regimen in Claudin-Low Breast Cancer
Abstract
Jun Chang,1,2 Ling Hong,2 Yaozhong Liu,3 Yiwen Pan,2 Hao Yang,2 Wenrui Ye,3 Keli Xu,4 Zhijian Li,1 Shubing Zhang1,2,5,6 1Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, People’s Republic of China; 3Xiangya Medical School, Central South University, Changsha, Hunan 410013, People’s Republic of China; 4Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA; 5Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, Hunan 410013, People’s Republic of China; 6Breast Cancer Research Center, School of Life Sciences, Central South University, Changsha, Hunan 410013, People’s Republic of ChinaCorrespondence: Zhijian LiDepartment of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, People’s Republic of ChinaTel +8613787314214Email [email protected] ZhangDepartment of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, People’s Republic of ChinaTel +861397589680Email [email protected]: Molecular targeting is a powerful approach for aggressive claudin-low breast cancer (CLBC). Overexpression of PI3K catalytic subunit gamma (PIK3CG) in human CLBC is offering a promising opportunity for targeted therapies. We utilized a specific inhibitor of PIK3CG combined with paclitaxel (PTX) to treat CLBC cells in vitro and in vivo.Patients and Methods: The tumor cells growth and apoptosis in vitro were analyzed by CCK8, plate clone formation assay, tumorsphere assay, Hoechst staining and flow cytometry. The invasion and metastasis ability of tumor cells in vitro were investigated by wound healing and transwell experiments. Critical gene expression levels were checked by qRT-PCR and Western blot. Xenograft models with CLBC cell lines in SCID mice were established to investigate the effect of combined drugs in vivo.Results: We identified that PIK3CG was a potential therapeutic target for CLBC patients. Targeting PIK3CG potentiated CLBC cells growth inhibition in 2D and 3D cultures by PTX. Inhibition of PIK3CG activation could enhance CLBC cells apoptosis and migration suppression induced by PTX. Manipulating autophagy was a validated approach for the use of PIK3CG inhibitor. Using CLBC xenograft mice model, we found that CLBC tumors in vivo could be well treated by combined drugs of PIK3CG inhibitor and PTX.Conclusion: We demonstrated that PIK3CG was a potential target for the therapy of CLBC and inhibition of PIK3CG activation could reinforce the therapeutic effect of this aggressive disease by PTX. The combined use of PIK3CG inhibitor and PTX might be a potential regimen for treating this subtype of breast cancer.Keywords: PIK3CG, paclitaxel, claudin-low breast cancer, combined drugs, targeted therapy
