Yin Li-Rong, Chen Ze-Xiong, Zhang Shi-Jun, Sun Bao-Guo, Liu Yong-Dong, Huang Hong-Zhong
Department of TCM, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
World J Gastroenterol. 2008 Jan 7;14(1):108-13. doi: 10.3748/wjg.14.108.
To explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in liver of athymic mice with hepatocellular carcinoma (HCC) and the effect of Fuzheng Jiedu Decoction (FJD).
Forty eight male BALB/c athymic mice models were built by Bel-7402 with an indirect method. After 24 h of postoperation, the 48 athymic mice were distributed randomly into 4 groups: A, B, C, D, each group had 12 athymic mice. Group A were were treated by intragastric administration with FT207 (Tegafur) for 4 wk. Group B, C and D were treated by intragastric administration with FJD (complex prescription of Chinese crude drug) that had been delegated into 3 kinds of density as the low, middle, and high for 4 wk. At last, athymic mice were put to death, live time, volume of tumors, exponent of tumors and the tumor metastasis in livers were observed; and PTEN was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry.
Four weeks later, the total survival rate in treatment group (A + B + C) was 50% and higher than the control group (0%) treated by FT207, (P < 0.01). The survival rate in group A, B, C was higher than in group D, and except group A with D, there was significant differences (Fisher's Exact Test P = 0.05 or 0.01). And no differences were observed between the treatment groups and the control group in volume of tumors and exponent of tumors (P > 0.05). Tumor metastasis in livers of the treatment group was less than the controls (Fisher's Exact Test, P = 0.021). The result of immunohistochemistry showed that the intensity of PTEN in latero-cancer tissue was the highest, and then the hepatic tissue, the lowest was cancer tissue (Kruskal-Wallis test, chi2 = 60.67, P = 0.000). It also showed that the intensity of PTEN in treatment groups (A, B, C) was higher than the control group (D) (F = 5.90, P = 0.002 in hepatic tissue and F = 15.99, P = 0.000 in latero-cancer tissue and chi2 = 26.08, P = 0.000 in cancer tissue), and group B is the highest in the treatment groups (P < 0.05, r = 0.01. respectively). However, there was no significant statistic difference between group A and group C (P > 0.05).
FJD can prolong the survival time and decrease tumor metastasis in livers of these experimental mice. Mechanisms of FJD healing HCC may partially be explained by enhancing the expression of PTEN in liver.
探讨10号染色体缺失的磷酸酶和张力蛋白同源物(PTEN)在无胸腺小鼠肝癌(HCC)肝脏中的表达及扶正解毒方(FJD)的作用。
采用间接法用Bel-7402建立48只雄性BALB/c无胸腺小鼠模型。术后24小时,将48只无胸腺小鼠随机分为4组:A、B、C、D组,每组12只。A组用替加氟(FT207)灌胃治疗4周。B、C、D组用已分为低、中、高3种浓度的扶正解毒方(中药复方)灌胃治疗4周。最后,处死无胸腺小鼠,观察存活时间、肿瘤体积、肿瘤指数及肝脏肿瘤转移情况;采用免疫组化法检测肝组织、癌旁组织及癌组织中的PTEN。
4周后,治疗组(A+B+C)的总生存率为50%,高于替加氟治疗的对照组(0%),(P<0.01)。A、B、C组的生存率高于D组,除A组与D组外,差异有统计学意义(Fisher精确检验P=0.05或0.01)。治疗组与对照组在肿瘤体积和肿瘤指数方面无差异(P>0.05)。治疗组肝脏肿瘤转移少于对照组(Fisher精确检验,P=0.021)。免疫组化结果显示,癌旁组织中PTEN的表达强度最高,其次是肝组织,癌组织中最低(Kruskal-Wallis检验,χ2=60.67,P=0.000)。还显示治疗组(A、B、C)中PTEN的表达强度高于对照组(D)(肝组织中F=5.90,P=0.002;癌旁组织中F=15.99,P=0.000;癌组织中χ2=26.08,P=0.000),且B组在治疗组中最高(P<0.05,r=0.01)。然而,A组与C组之间无显著统计学差异(P>0.05)。
扶正解毒方可延长这些实验小鼠的存活时间并减少肝脏肿瘤转移。扶正解毒方治疗肝癌的机制可能部分是通过增强肝脏中PTEN的表达来解释。