The Effect of Dexamethasone on the Chemosensitivity of Colon Carcinoma Cells to L-OHP and 5-Fu Treatment / 中国肿瘤临床

ABSTRACT

Objective: To examine the expression of glucocorticoid receptor in human colon cancinoma tis-sues and call lines and to explore the survival of colon cancer cell lines treated with dexamethasone alone or in combination with 5-Fu and L-OHP in a way of dexamethasone pretreatment or co-administration in vitro.Methods: The expression of glucocorticoid receptor was detected in 61 cases of colon cancer tissue samples and 4 types of colon cancer cell lines by immunohistochemistry. Apoptosis was detected by Hoechst33342 staining and flow cytometry. MTT assay was employed to detect the chemosensitivity of colon carcinoma cells to L-OHP and 5-Fu with dexamethasone pretreatment for 24 hours or co-administretion. Results: Positive GR expression was found in 57.3% colon cancer tissue samples and in Lovo and HCT-116 cell lines, not in HT-29 and SW-480. Apoptosis was detected in GR-expressed Lovo and HCT-116 cells at 72 hours after 1×10~(-4)mol/L Dex treatment, and the rates of apoptosis were higher than those in the control groups without Dex (P<0.01),GR-negative cells, HT-29 and SW-480 even treated with 1 × 10~(-4)mol/L Dex for 72 hours. Pretreatment and co-administration for Lovo cells with 1×10~(-4)mol/L Dex could decrease the IC50 of L-OHP from 13.7±11.3μg/mL to 5.9±0.6μg/mL and 4.8±0.7μg/mL, respectively. IC50 of 5-Fu was decreased from 72.2±8.1 μg/mL to 21.1±4.1μg/mL and 18.6±4.0μg/mL, respectively. Conclusion: There is expression of glucocorticoid receptor in part of colon carcinoma tissue samples and cell lines. Apoptosis does occur in GR-expressed Lovo and HCT-116 cells induced by dexamethasone in vitro. Pretreatment for 24h and co-administration with Dex can increase the chemosensitivity of Lovo cells to L-OHP and 5-Fu.