Effects of GRP78 on sensibity of gemitabine on patients with NSCLC / 吉林大学学报(医学版)

ABSTRACT

Objective: To investigate the relationship between the expression of glucose-regulated protein 78 (GRP78) and gemcitabine chemotherapy in the patients with non-small cell lung cancer (NSCLC) and the effects of GRP78 on the viability of lung adenocarcinoma SPCA1 cells and the chemosensitivity of gemcitabine, and to elucidate its mechanisms. Methods: The positive expression rates of GRP78 in 32 cases of cancer tissue of the NSCLC patients were detected by immunohistochemical staining. The SPCA1 cells with high expression of GRP78 were selected as the subjects. RNA interference technique was used to down-regulate the expression of GRP78 in SPCA1 cells (interference group) and the cells treated with shNC were used as control group. MTT assay was used to detect the viabilities of SPCA1 cells in various groups. Negative control group, interference group, control + gemcitabine group, and interference+ gemcitabine group were set up; colone formation assay was used to detect the colone formation rates of SPCA1 cells in various groups; Western blotting method was used to detect the expression amount of Akt, p-Akt, PI3K, and p-PI3K in the SPCA1 cells in various groups. Results: The immunohistochemical staining results showed that the positive expression rate of GRP78 in cancer tissue in the remission NSCLC patients was significantly higher than that in the no-remission NSCLC patients after treated with gemcitabine (P<0. 05). The MTT assay results showed that compared with negative control group, the viability of SPCA1 cells in interference group was decreased significantly (P<0. 05), and the viability of SPCA1 cells in interference + gemcitabine group was significantly decresed (P<0. 05). The Western blotting results showed that compared with negative control group, the expression amounts of p-Akt and p-PI3K in the SPCA1 cells in interference group were decreased, and the expression amounts of p-Akt and p-PI3K in the SPCA1 cells in interference+gemcitabine group were decreased significantly. Conclusion: Interference of GRP78 may increase the sensitivity of gemcitabine to chemotherapy, and GRP78 may reduce the sensitivity of NSCLC patients to gemcitabine through PI3K/Akt pathway.