Antitumor effect of Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, combined with cytotoxic agent on murine hepatocellular carcinoma

Abstract

To investigate the inhibitory effect of gefitinib combined with cytotoxic agent cisplatin (CDDP) on hepatocellular carcinoma (HCC). Female Kunming mice and H22 hepatocarcinoma cells were used. Gefitinib at daily dose of 100 mg/kg body weight (BW) or lecithin liquid was given by gastrogavage once a day for 5 or 10 successive days. CDDP or normal saline (NS) was administered intraperitoneally (i.p.) once a day for 5 successive days. Mice were randomly divided into control group (lecithin, or NS, i.p.), CDDP group (daily dose, 1.2 mg/kg BW; d1-5, or d6-10), Gefitinib (d1-5, or d6-10, or d1-10), and Gefitinib combined with CDDP groups. The inhibitory rate (IR) of tumor, net BW, spleen index (SI), thymus index (TI) and the amount of peripheral blood cells of mice were detected on the 12th experiment day. The growth of HCC in mice was inhibited by Gefitinib alone (IR: 41% in d1-10 group and 30% in d1-5 group, respectively) or CDDP alone (IR: 32-54% in d1-5 group or d6-10 group). The highest inhibitory effect (IR: 56%) on HCC growth was observed in Gefitinib (d1-10) combined with CDDP (d1-5) group. Higher inhibition was also observed in CDDP (d1-5) followed by Gefitinib (d6-10) group than that in Gefitinib (d1-5) followed by CDDP (d6-10) group (IR: 61% vs 36%, P < 0.01) in the independent study. Net BW, SI, TI and the amount of blood cells of mice in Gefitinib alone group were not significantly different from those in control groups. Gefitinib can significantly inhibit the growth of murine H22 hepatocellular carcinoma. If Gefitinib is used after CDDP treatment in animal experiments, the inhibitory effect could be enhanced.