¹²⁵I Seeds External Irradiation In Combination With EGFR Inhibitor C225Induces Apoptosis Of Gastric Cancer Cells (MNK-45)and Influences The Expression Of Bcl-2and Bax

Objective To study125I seeds continuous external irradiation combined with EGFR inhibitor C225influence the effects of apoptosis-inducing in human gastric cancer cell line MNK-45and the expression of apoptosis-regulated gene Bax and Bcl-2,to exploe the feasibility of the combination of this two metheds in the therapy of human gastric cancer.Methods The experiment consists of control group, EGFR inhibitor group, irradiation group, and combination group, choosing the125I seeds(0.4mCi) to build the irradiation devices. Human gastric cancer cell MNK-45of irradiation group, and combination group were accepted continuous irradiation in presence or absence of C225(2000ug/ml) in this device.The control group and the EGFR inhibitor group were not accepted irradiation in same devices.72hours later, the gastric cancer cells in each group were collected. The cells growth condition was analyzed by Cytometry. To observe the changes of the tumor cells ultrastructural by TEM.The cells rates of apoptosis and cell cycle was determined by flow cytometry (FCM). And the change of expression of Bcl-2/Bax mRNA was detected by RT-PCR.Results Compared with the controls group, the growth velocity of the MNK-45cell of each treatment group which was analyzed by Cytometry was step down dramatically(P<0.05),and the quantity of tumor cell in combination group was less than the drug group and irradiation group(P<0.05); we can observe the early-mid-late period cell apoptosis in the experiment group by TEM,rare cell apoptosis were found in the control group;Flow cytometry showed that the apoptosis rates of each treatment group was higher than that in control group (P<0.05). And the irradiation plus inhibitor led to more apoptosis of MNK-45cells than the irradiation plusd inhibitor worked alone; Flow cytometry showed that the cells proportion of G0/G1in each treatment group was more than the control group(P<0.05),and the cells proportion of S in each treatment group was less than the control group (P<0.05). this phenomenon in combination group was the most strongest(.P<0.05);The expression level of Bcl in each treatment group was decreased and the expression level of Bax in each treatment group was enhanced obviously t(P<0.05), this phenomenon in combination group was further enhanced(P<0.05).with the decrese of Bcl-2expression and the increase of Bax expression by RT-PCR detection,The ratio of Bax to Bcl-2in each treatment group was higher than that in control group(.P<0.05).And this phenomenon was most significantly display in combination group.Conclusions1.125I seeds external irradiation combined with EGFR inhibitor C225could strengthen the effects of apoptosis-inducing in human gastric cancer cell line MNK-45and thire effects was stronger than125I seeds or C225used longly;2.125I seeds external irradiation combined with EGFR inhibitor C225could lead to the apoptosis rates of tumor cells was incrsead significantly and the cells cycle was changed, thire effects was stronger than125I seeds or C225used longly;3.125I seeds external irradiation combined with EGFR inhibitor C225could decrease the expression of Bcl-2and increase the expression of Bax in MNK-45cells,and so the ratio of Bcl-2to Bax was furtherly decreasd.