Abstract

Knockdown of Gene SLC7A11 in OVCAR8 Cells Increases Susceptibility of Cells to Anti-cancer Drugs

Student: Yuxiao Tan
Mentor: Jin-Xiong She (Augusta University)

Cancer cells derive from cells with multiple gene mutations and end up with infinite life span. Some mutations lead to anti-cancer drug resistance or increased level of expression of other genes, such as SLC7A11. In this project, the expression level of SLC7A11 was decreased using siRNA. We found that cancer cells with decreased expression level of SLC7A11 have lower survival rate under anti-cancer drugs treatment.

Multiple genes have increased expression level in cancer cells, some of which correlate with resistance to anti-cancer drugs and poorer patient survival rates. SLC7A11 is a gene that codes for the membrane protein xCT, a member of a heterodimeric Na+ independent anionic amino acid transport system that highly specific for cystine and glutamate. Downstream to the transportation pathway, cystine is rapidly reduced to cysteine, which is a precursor of synthesis of Glutathione (GSH). Production of GSH limits over accumulation of reactive oxygen species (ROS) and prevents ferroptosis, a non-apoptotic form of cell death. SLC7A11 has been shown with increased expression level in majority types of vivo cancer cells. Limiting GSH synthesis by decreasing SLC7A11 expression becomes a potential pathway of killing cancer cells. In this project, siRNA screening tested six different siRNA sequences, and knockdown efficiency was determined using RT-qPCR. OVCAR8 cell viability test after drug screening indicated that treatment with selected SLC7A11 sense siRNA had markedly decreased survival rate in combination with drugs than either drugs or knockdown alone. Based on the results of drug screening, a synergic effect was demonstrated between SLC7A11 knockdown and drug treatment. Thus, we concluded that knockdown of SLC7A11 could increase the susceptibility of OVCAR8 cells to anti-cancer drugs and promote drug efficiency.