Remaining tumour cells after combined effect of epidermal growth factor and gemcitabine for bladder cancer xenografted tumor

Abstract

Objective To study the combined effect of epidermal growth factor (EGF) and Gemcitabine (GEM) for bladder cancer xenografted tumor, preliminary mechanism of action, and character of the remaining tumour cell. Methods Bladder cancer xenografted tumor model was established. Treated by united therapy group and merely chemotherapy group, the bladder cancer BIU-87 cells were tested for the ability to form tumors, tumor control rate, the expression of proliferation cell nuclear antigen (Ki-67), Cyclins (Cyclin A, Cyclin B, Cyclin D, Cyclin E), the CD44+ positive proportion in bladder cancer cells, and tumorigenic ability. Results Tumor control rate of bladder cancer xenografted tumor in EGF+ GEM group was apparently higher than that in GEM group, respectively 70.7% and 40% (P<0.05). The expression of Ki-67 in EGF+ GEM group and GEM group were respectively (52.76±6.36)% and (37.01±4.45)% (P<0.05). The expression level of Cyclins (Cyclin A, Cyclin B, Cyclin D, Cyclin E) of bladder cancer xenografted tumor in EGF+ GEM group were apparently lower than these in GEM group, respectively (33.76±4.94)%, (53.67±5.37)%; (31.26±4.67)%, (49.46±5.35)%; (31.85±5.56)%, (54.58±7.67)%; (43.01±6.45)%, (66.45±7.09)% (P<0.05). The CD44+ positive proportion of bladder cancer xenografted tumor in EGF+ GEM group were apparently higher than these in chemotherapy group, respectively (9.12±0.49)% and (5.39±0.32)% (P<0.05). Tumorigenic ability of the remaining tumour cells in EGF+ GEM group were apparently higher than these in GEM group, (1 731.24±110.34), (2 298.84±102.56) mm3 (P<0.05). Conclusion EGF can enhance the sensitivity of GEM to bladder cancer cells, and the possible mechanism is that EGF induces these bladder cancer cells in stationary phase into cell proliferative phase. The remaining tumor cells treated by EGF+ GEM may be new tumor cell subpopulation with low Cyclins and stronger tumorigenic ability. Key words: Epidermal growth factor; Gemcitabine; New tumor cell subpopulation