Inhibitory Effect Of Huangqi Injection On Human Nasopharyngeal Carcinoma Cell Line CNE2 Xenograft In Nude Mice

OBJECTIVE: To study the effect of Huangqi Injection on tumor growth inhibition of human nasopharyngeal carcinoma cell strain CNE2 xenograft in BALB/c nude mice, and explore the possible mechanisms.METHODS: CNE2 cells were injected subcutaneously into nude mice to establish model of transplanted tumor. Thirty five model nude mice were divided randomly into five groups treated with intraperitoneal injection, viz the model group given normal sodium 10ml/(kg·d), the positive control group given Cisplatin 30mg/m2 every fourteen days and given normal sodium 10ml/(kg·d) in other days, and three treatment groups given Huangqi injection 10.4, 5.2 and 2.6g/(kg·d) respectively. Above administrations for groups lasted 4 weeks. The inhibitory effect of Huangqi injection on the growth of tumors in nude mice was observed and the inhibitory rate was calculated. The pathological changes of tumor tissues dyed by HE staining were observed with light microscope. The immunohistochemistry assay was made to detect the expression levels of P53, Bcl-2 and Bax protein in tumor tissues from groups. And the expression levels of p53 mRNA in tumor tissues were determined by FQ-PCR.RESULTS: 1. After four weeks'treatment, the volumes of tumors in nude mice from the model group, the Cisplatin group, the high dose group of Huangqi injection, the middle dose group of Huangqi injection and low dose group of Huangqi injection were 1514.8±252.1mm3, 910.6±349.9mm3, 1043.7±507.2mm3, 1113.2±365.3mm3 and 1441.7±271.9mm3 respectively. Compared with the model group, the tumor volumes in the Cisplatin group were smaller (P<0.01), and the tumor volumes in both the high dose group of Huagnqi injection and the high dose group of Huagnqi injection were smaller (P<0.05). And yet the low dose group of Huangqi injection was not distinctly different from the model group in the tumor volume (P>0.05).2. After four weeks'treatment, the weights of tumors in nude mice from the model group, the Cisplatin group, the high dose group of Huangqi injection, the middle dose group of Huangqi injection and low dose group of Huangqi injection were 2.08±0.14g, 0.58±0.06g, 1.25±0.30g, 1.44±0.34g, 1.84±0.58g and 1.44±0.34g respectively. Compared with the model group, the tumors in the Cisplatin group, the high dose group of Huagnqi injection and the high dose group of Huagnqi injection were lighter (P<0.01). And no marked difference was found between the low dose group of Huangqi injection and the model group in the tumor weight (P>0.05). The inhibitory rates of the Cisplatin group, the high dose group of Huangqi injection and the middle dose group of Huangqi injection were 72.12%, 39.90%, 30.77% respectively.3. HE staining showed that the tumor cell nucleoli in the model group were bigger than that in the Cisplatin group, the high dose group of Huangqi injection and the middle dose group of Huangqi injection. Both Cisplatin and Huangqi injection could induce apoptosis of carcinoma cells and improve histopathologic changes of tumor tissues. 4. In tumor tissues from the model group, the high dose group of Huangqi injection and the middle dose group of Huangqi injection, the expression levels of P53 protein were 49.63%, 37.11% and 40.43% respectively. The expression levels of P53 protein in tumor tissues from both the high dose group of Huangqi injection and the middle dose group of Huangqi injection were lower than those from the model group (P<0.05). And there were no significant difference among the model group, the Cisplatin group and the low dose group of Huagnqi injection in the expression levels of P53 protein in tumor tissues (P>0.05). In tumor tissues from the model group, the high dose group of Huangqi injection and the middle dose group of Huangqi injection, the expression levels of Bcl-2 protein were 50.27%,21.81% and 26.27% respectively. The expression levels of Bcl-2 protein in tumor tissues from the high dose group of Huangqi injection and the middle dose group of Huangqi injection were lower than those from the model group (P<0.01). Whereas, the expression levels of Bax protein in tumor tissues from five groups were immunohistochemical negativity.5. No significant difference was found among five groups in the expression levels of p53 mRNA in tumor tissues (P>0.05).CONCLUSION: The results suggest that Huangqi injection shows inhibition effect on the growth of human nasopharyngeal carcinoma cell strain CNE2 xenograft in BALB/c nude mice, which may be related to the decrease of expression levels of P53 and Bcl-2 protein in the tumor tissue and the induction of carcinoma cells apoptosis.