Antitumor Effects Of Epidermal Growth Factor Receptor (EGFR), ZD1839, Combined With Cisplatin On Murine Cervical Carcinoma U14

Background:Cervical cancer has the highest incidence in Gynecological malignant carcinomas. Radiotherapy in combination with chemotherapy plays an important role in the clinical treatment, but the toxicities were too severe.Objective: To observe the combination effects of cisplatin and ZD1839 on apoptosis induction in mice bearing cervical varcinoma U14 and to provide theoretical basis for clinical cervical cancer treatments.Methods:615-strain mice with U14 were randomly divided into seven groups: control group,cisplatin ( DDP ) group, ZD1839 group,ZD1839 combined with DDP early (ZD1839+DDP d1-4) group,and ZD1839 combined with DDP lately (ZD1839+DDP d7-10) group.ZD1839 was given by daily gastrogavage for 10 days (day1-day10) at 100mg/kg in body weight(BW).DDP was given by daily intraperitoneal injection for 4 days(day1-day4,or day7-day10) at 2mg/kg in BW. After treatment, tumor diameter,tumor weight and the tumor growth inhibiting rate (IR) of each group were measured. The U14 cell apoptosis rate was assessed by FCM and TUNEL.Results:(1)All the detected index of the transplanted tumor in experimental group were significant inhibited Compared with control groups (P<0.01).(2)IR of tumor in ZD1839+DDP (D,E group) group was significantly higher than that in ZD1839 (B group) group and DDP(C group)group(P<0.05). The apoptosis rate of tumor in ZD1839+DDP (D,E group) group was markedly higher than that in ZD1839 (E group)group and DDP ( C group ) group (P<0.01). (3)The apoptosis rate of tumor inZD1839+DDP d1-4 (D group) group was higher than that in ZD1839+DDP d7-10(G group) group(P<0.05).Conclusion:(1) Combined with ZD1839, cisplatin could markedly inhibit the growth of the transplantation tumor of mice cervical cancer by inducing apoptosis. In other words,ZD1839 could enhance the inhibiting effect of cisplatin on mice cervical cancer. (2) ZD1839 combined with cisplatin earlier showed more significant effects on inducing the carcinoma cell apoptosis than ZD1839 combined with cisplatin later.(3)This provides us theoretical basis for the combination chemotherapy between ZD1839 and cisplatin in the patients of recurrent cervical carcinoma or advanced stage or being too old to tolerate surgery.