Genotype change and mechanism of drug resistance of metastatic non-small cell lung cancer

Abstract

Objective To investigate the difference of genotype between primary tumor and metastatic tumor and the mechanism of chemoresistance in metastatic non-small cell lung cancer (NSCLC). Methods The mRNA expression level of frequently mutated genes in primary and metastatic tumors was detected by quantitive real-time quantitative polymerase chain reaction (Real-time PCR). Real-time PCR was applied to the primary tumor (P1), culture-expanded P5 and P10 cells. Scratch and Transwell migration assays were performed to study the migration ability. Cells in different groups were treated with chemotherapeutics. The difference of high frequency mutated gene was detected after three generations. Scratch assays and Transwell migration assays were performed to study the migration ability. Results The Real-time PCR results showed that the RB1 expression (0.72±0.05, (P=0.013) in primary tumor decreased and the expression of RB1 (0.75±0.02, P=0.004) and p53 (0.23±0.07, P=0.021) in metastatic tumor decreased also. After expanded, cultured cells didn’t show difference in the results of Real-time PCR, Transwell migration assay and scratch assay. When exposed to chemotherapy drugs, the expression of KRAS (3.43±0.31, P=0.002) increased in primary tumor, phosphatase and tensin homologue deleted on chromosome ten (PTEN) (0.43±0.25, P= 0.015) expression decreased significantly and migration capability was enhanced (P=0.048, 0.011). Conclusion The gene mutation in primary tumor was different with metastatic tumor of NSCLC, which occurred during the invasive process. Cancer cells could produce chemoresistance through inducing novel mutation. Key words: Non-small cell lung cancer; Metastatic tumor; Gene mutation; Chemoresistance