MACC1 INVOLVED IN THE REGULATION OF RESISTANCE OF HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2–POSITIVE GASTRIC CANCER CELLS TO TRASTUZUMAB

GUOFEI ZHANG, KEFU HU, RONG YU, GANG SU, XIN XIONG, DAQIAN HU, ZHIHONG ZHANG #

Department of Oncology, Gong’an County People’s Hospital

Objective: We sought to analyze whether the mechanism of the MACC1 gene involved in human epidermal growth factor receptor 2 (HER2)-positive gastric cancer cells regulates trastuzumab-resistant gastric cancer.

Methods: Cell lines sensitive to trastuzumab and positive for MACC1 and HER2 expression were screened from human gastric cancer cell lines, drug-resistant cell MKN45/TR was established by a stepwise dose-increase method, and the expression level of MACC1 protein in trastuzumab-resistant cells was detected using Western blot. The inhibition rate of cell proliferation after trastuzumab treatment for 72 hours was detected using MTT.

Results: Drug-resistant cell MKN45/TR was established using a stepwise dose-increase method. Half-maximal inhibitory concentration and resistance index of cell trastuzumab were detected during the induction period. The induction time was five months and the final induction concentration was 2,500 μg/mL. Additionally, the half-maximal inhibitory concentration of trastuzumab was 295.15 μg/mL and the drug resistance index was 9.67. Western blot detection results showed that, as compared with cells without drug resistance, the MACCI protein level of trastuzumab- resistant cells obviously increased. NCI-N87/TR and MKN45/TR were given transinfection using MACC1 interference and empty vector and were treated using different concentrations of trastuzumab. The cell inhibition rate was detected using the MTT method. Under the function of trastuzumab at concentrations of 20 μg/mL, 80 μg/mL, and 160 μg/mL, there was statistical significance between the interference group and the control group with respect to the inhibition rate of cell proliferation (P<0.05).

Conclusion: MACC1 participates in the regulation of trastuzumab in gastric cancer cells. The expression level of MACC1 protein cells in transinfection resistance increases, thus interfering MACC1 in resistance cells and reversing the resistance of MACC1.