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Establishment of gefitinibresistant human colon carcinoma cell line HT29/ZD and its drug resistant mechanism
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Abstract:
To establish a gefitinibresistant human colon carcinoma HT29/ZD cell line and to preliminarily study its drug resistance mechanisms. Methods: Gefitinibresistant HT29/ZD was induced by stepwise selection after exposure to increasing doses of gefitinib. IC50were determined by MTT assay and the resistance index (RI) was calculated. Cell growth curves were plotted and the double times were calculated by cell counting assay. Distribution of cell cycles were detected by flow cytometry. Crossresistance profiles of HT29/ZD to 5Fu, DDP, LOHP, and CPT11 were tested by MTT assay. Expression levels of IGFRa, PIGFR and Pgp were determined by immunocytochemistry method. Results: A genfibinibresistant human colon carcinoma cell line HT29/ZD has been established successfully, with the RI being 2667. The doubling times of HT29/ZD and HT29 cells were 33.25 and 37.7 h, respectively. Flow cytometry demonstrated that HT29/ZD cells of phase S and G2M were increased, but those of G0/G1 phase were reduced. We also found that, compared to HT29 cells, HT29/ZD cells had an increased sensitivity to 5Fu, DDP （P>005）, and showed certain resistance to CPT11（P>0.05）, but had a significantly increased sensitivity to LOHP. Immunocytochemical analysis demonstrated that HT29 and HT29/ZD cells had a similar expression of Pgp （P>0.05）. HT29/ZD cells had a lower expression of IGF1Ra (P<0.01) than HI29 cells but a higher expression of phosphoIGF1R (P<001). Conclusion:HT29/ZD has no multidrug resistance like traditional anticancer drugs. PhosphoIGF1R of HT29/ZD has an increased activity, which might be one of the mechanisms for the acquired resistance of HT29/ZD. Pgp has no relationship with acquired resistance to gefitinib.
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