Therapeutic potential of anti-PIK3CG treatment for multiple myeloma via inhibiting c-Myc pathway

Xiaotang Di; Yiwen Pan; Jinhua Yan; Jing Liu; Doudou Wen; Hao Jiang; Shubing Zhang

doi:10.1016/j.heliyon.2023.e23165

Therapeutic potential of anti-PIK3CG treatment for multiple myeloma via inhibiting c-Myc pathway

Heliyon. 2023 Dec 6;10(1):e23165. doi: 10.1016/j.heliyon.2023.e23165. eCollection 2024 Jan 15.

Authors

Xiaotang Di¹, Yiwen Pan^{1

2}, Jinhua Yan¹, Jing Liu³, Doudou Wen¹, Hao Jiang⁴, Shubing Zhang^{1

5}

Affiliations

¹ Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan, 410013, China.
² The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, 710061, China.
³ Molecular Biology Research Center, School of Life Sciences, Central South University, Changsha, Hunan, 410013, China.
⁴ Department of Biomedical Informatics, School of Life Sciences, Central South University, Changsha, Hunan, 410013, China.
⁵ Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, Hunan, 410013, China.

Abstract

Multiple myeloma (MM) is a malignant plasma cell disease. The activity of PIK3CG (PI3K catalytic subunit γ) is regulated directly by G-protein-coupled receptor and has been confirmed to be highly expressed in MM cells. This study aimed to determine the effect of pharmacological inhibition of PIK3CG on MM. We found that different concentrations of the PIK3CG inhibitor AS-605240 could suppress the growth of MM cell lines and the expression of c-Myc. The combination of PIK3CG inhibitor and the chemotherapy Melphalan could effectively inhibit the proliferation and migration of MM cells, promote the cell apoptosis, and decrease the ratio of Bcl-2/Bax and the expression of vimentin. The expression of proto-oncogene c-Myc was decreased and the sensitivity of cells to chemotherapeutic drugs was enhanced. Collectively, PIK3CG regulates growth of MM via c-Myc pathway, thus emerging as a promising molecular targeted therapy.

Keywords: Melphalan; Multiple myeloma; PIK3CG; Targeted therapy; c-Myc.