Metformin inhibits the growth of hypopharyngeal carcinoma xenografts in nude mice model

Abstract

Objective:To investigated the effect of metformin on growth inhibition of hypopharyngeal carcinoma xenograft in nude mice and to study the theoretical basis of metformin for the treatment of hypopharyngeal carcinoma in clinical.Method:①To observe the course of metformin treatment, there were no severe adverse effects among the xenograft mice. ②After 28 days treatment, the average volumes of hypopharyngeal carcinoma xenografts of the metformin treated groups were significantly low compared with that of the control group.〖JP2〗The inhibition ratio of metformin at the concentration of 40 mg/(kg•d) and 200 mg/(kg•d) to the growth of tumor was 23.30%±7.17% and 40.51%±9.25%, respectively.③The aver ageoptical density(OAD) of AMPK in tumors of the control, met40 and met200 group was 0.246±0.038, 0.262±0.046, and 0.308±0.087, respectively. The OAD of p21 was 0.288±0.065, 0.305±0.091, and 0.477±0.114, respectively. And the OAD of cyclin D1 was 1.608±0.101, 0.781±0.055, and 0.711±0.046, respectively. Both the OAD of AMPK and p21 in met40 and met200 group were observably higher than those of the control group (P< 0.05). But the OAD of cyclin D1 in met40 and met200 group were remarkably lower than the control group (P< 0.05). ④The Western Blot drawed the consistant trend variation with immunohistochemical analyses. The gray value of AMPK in tumors of the control,met40 and met200 group was 0.641±0.042, 1.124±0.085, and 1.783±0.128; The gray value of p21 was 0.474±0.027, 0.594±0.063, and 0.970±0.079; The gray value of cyclin D1 was 1.608±0.101,0.781±0.055, and 0.711±0.046.Result:①To observe the course of metformin treatment, there were no severe adverse effects among the xenograft mice. ②After 28 days treatment, the average volumes of hypopharyngeal carcinoma xenografts of the metformin treated groups were significantly low compared with that of the control group.〖JP2〗The inhibition ratio of metformin at the concentration of 40 mg/(kg•d) and 200 mg/(kg•d) to the growth of tumor was 23.30%±7.17% and 40.51%±9.25%, respectively.③The aver ageoptical density(OAD) of AMPK in tumors of the control, met40 and met200 group was 0.246±0.038, 0.262±0.046, and 0.308±0.087, respectively. The OAD of p21 was 0.288±0.065, 0.305±0.091, and 0.477±0.114, respectively. And the OAD of cyclin D1 was 1.608±0.101, 0.781±0.055, and 0.711±0.046, respectively. Both the OAD of AMPK and p21 in met40 and met200 group were observably higher than those of the control group (P< 0.05). But the OAD of cyclin D1 in met40 and met200 group were remarkably lower than the control group (P< 0.05). ④The Western Blot drawed the consistant trend variation with immunohistochemical analyses. The gray value of AMPK in tumors of the control,met40 and met200 group was 0.641±0.042, 1.124±0.085, and 1.783±0.128; The gray value of p21 was 0.474±0.027, 0.594±0.063, and 0.970±0.079; The gray value of cyclin D1 was 1.608±0.101,0.781±0.055, and 0.711±0.046.Conclusion:Metformin can suppress the growth of hypopharyngeal carcinoma xenograft in nude mice and inducing tumor cell apoptosis without any severe adverse effects.