RESUMO
Objective To explore the expression of cullin 4A (CUL4A) in cholangiocarcinoma tissues and its clinical significance.Methods Primary fresh cholangiocarcinoma tissues (n =35) and normal bile duct tissues (n =15) from patients who underwent curative surgery in Binzhou People's Hospital of Shandong Province from February 2011 to December 2013 were collected.The expressions of CUL4A mRNA were detected by quantitative real-time PCR (qRT-PCR).Then,cholangiocarcinoma tissues (n =72) and normal bile duct tissues (n =36) from patients who underwent curative surgery in Binzhou People's Hospital of Shandong Province from January 2008 to January 2014 were collected.The expressions of CUL4A protein were tested by immunohistochemistry.The relationships between the expression of CUL4A and the patients' clinicopathologic features and prognosis were analyzed.Results The expression of CUL4A mRNA in cholangiocarcinoma tissues was obviously higher than that in normal bile duct tissues (3.876 ±0.975 vs.1.216 ±0.265),and the difference was statistically significant (t =12.23,P ＜ 0.001).The positive rates of CUL4A protein in cholangiocarcinoma and normal bile duct tissues were 70.8％ (51/72) and 2.8％ (1/36) respectively,and the difference was statistically significant (x2 =44.524,P ＜ 0.001).The expression of CUL4A protein in cholangiocarcinoma was related to the differentiated degree (x2 =4.341,P =0.037),neural invasion (x2 =8.326,P =0.004),TNM stage (x2 =7.745,P =0.005),lymph node metastasis (x2 =3.869,P =0.049) and vascular invasion (x2 =5.555,P =0.018).Survival analysis results showed that the median survival time of CUL4A positive patients was significantly shorter than that of CUL4A negative patients (32.40 months vs.51.30 months),and the difference was statistically significant (x2 =6.561,P =0.011).Conclusion The expression of CUL4A in cholangiocarcinoma tissues is higher than that in normal bile tissues.CUL4A plays an important role in the process of tumor invasion and metastasis and indicates poor prognosis,which may become a potential target for the diagnosis and therapy of the cholangiocarcinoma.
RESUMO
Objective To investigate of the MMI-166 on the expression of MMP-2,MMP-9 and the cell apoptosis of nude mouse xenografts of SW1990 human pancreatic cancer cells.Methods Establishment of control and experimental groups,randomly,the human pancreatic cancer xenograft model of SW1990 was constructed.The control group was treated with normal saline,and experimental group was treated with MML-166 (200 mg · kg-1 · d-1).The tumor volume and tumor inhibition rate was measured by vernier caliper through length and short diameter.The expression of MMP-2 and MMP-9 protein was observed using immunohistochemistry in the tumor tissues.Apoptosis index was detected by deoxynucleotidyl transferase-mediated nick end labeling (TUNEL method).Results The tumor volume of MMI-166 group (1252.30± 464.84) mm3 was less than the control group (2241.82±208.06) mm3,significantly.The inhibition rate was 34.47％ between the experimental groups (treat with MMI-166) (1.42±0.15) g and control group (2.17±0.20) g.The expression of MMP-2 (2.80 ± 1.10) ％ and MMP-9 (2.60 ± 1.52) ％ protein was significantly downregulated in MMI-166 group,compared with the control group.Apoptotic index in the experimental group (75.60±9.71) ％ was higher than the control group (17.40 ± 10.14) ％,significantly.Conclusion The mechanism of MMI-166 inhibiting pancreatic tumor growth and inducing apoptosis may be related to the suppression of MMP-2 and MMP-9 protein expression.