食管癌P-gp和P27表达水平及对生存的影响

目的:研究食管癌细胞多药耐药性和细胞周期调控因子表达水平及对患者生存期的影响。方法:用免疫组化方法检测了104例有随访资料的食管癌手术标本中癌细胞P-糖蛋白(P-gp)和细胞周期调控因子(P27)表达水平,并进行临床病理分析。结果:104例食管癌P-gp表达阴性70例(67.3%);阳性表达34例,其中轻度表达6例(5.7%)、中度表达18例(17.3%)、重度表达10例(9.6%)。P27表达阴性34例(32.7%);阳性表达70例,其中轻度表达7例(6.7%)、中度表达42例(40.4%)、重度表达21例(20.2%)。在生存3年以上组P-gp表达阳性占17.5%(10例),而3年内死亡组P-gp表达阳性占53.3%(24例),两组比较差异有非常显著性(P<0.0001)。P-gp过表达与癌细胞恶性生物学行为和死亡率成正相关。生存3年以上组P27表达阳性占75.8%(44例),而在3年内死亡组P27表达阳性占56.5%(26例),两组比较差异有显著性(P<0.05)。P27过表达与癌细胞恶性生物学行为和死亡率呈负相关。肿瘤的分化程度在生存组与死亡组比较差异有显著性(P<0.05)。肿瘤的浸润深度在生存3年以上组浸润全层仅占53.4%(31例),而在3年内死亡组浸润全层占82.6%(38例),两组比较差异有非常显著性(P<0.01)。淋巴结有无转移的生存组与死亡组比较差异有显著性(P<0.05)。临床分期在生存组与死亡组比较差异有显著性(P<0.05)。结论:P-gp过表达与癌细胞恶性生物学行为和死亡率成正相关。P27过表达与癌细胞恶性生物学行为和死亡率呈负相关。检测P-gp和P27表达水平可为临床提供选择化疗方案的参考依据。肿瘤的分化程度、浸润深度、淋巴结转移、临床分期是影响食管癌患者生存的重要因素。

Akt1/p27^(kip1) Pathway Mediates Inhibition of LXA_4 on TNF-α-induced Proliferation of Rat Mesangial Cells

Objective:To examine whether lipoxin A 4(LXA 4) has an inhibitory effect on tumor necrosis factor-α(TNF-α)-induced proliferation of glomerular mesangial cells of rat, and explore the molecular mechanisms of signal pathway in LXA 4 actions. Methods: Glomerular mesangial cells of rat were cultured and treated with TNF-α(10 ng/ml), with or without preincubation with LXA 4 at different concentrations. Cell proliferation was evaluated by monotetrazolium (MTT) colorimetric assay. The expression of cyclin E mRNA was measured by RT-PCR. Phosphorylated Akt1(Thr308) and p27 kip1 were analyzed by Western blotting. Results: TNF-α-stimulated proliferation of mesangial cells was inhibited by LXA 4 in a dose-dependent manner. The marked increments in cyclin E mRNA expression induced by TNF-α during proliferation of mesangial cells were down-regulated by LXA 4. Threonine phosphorylated Akt1 proteins at 308 site stimulated by TNF-α was reduced by LXA 4. TNF-α-induced decrements in expression of p27 kip1 proteins was ameliorated by LXA 4 in a dose-dependent manner. Conclusion: TNF-α-induced proliferation of rat mesangial cells can be inhibited by TXA 4 through the mechanism of Akt 1/p27 kip1 pathway-dependent signal transduction.

Prognostic Value of P-gp and p27 in Patients with Esophageal Squamous Cell Carcinoma

Objective： To evaluate the prognostic value of P-gp and p27 expression in patients with esophageal squamous cell carcinoma （ESC）. Methods： The expressions of P-gp and p27 were detected by immunohistochemistry in 104 cases of ESC, and the clinicopathological characteristics were analyzed as well. Results： The positive rate of P-gp expression in 104 cases of ESCs was 32.7%. The positive rate of P-gp expression in the group that survived over 3 years （17.5%） was significantly lower than that in the group died within 3 years （53.3%） （x^2=14.227, P〈0.001）. The positive rate of p27 expression in 104 cases of ESCs was 67.3%. The positive rate of p27 expression in the group that survived over 3 years （75.8%） was significantly higher than that in the group died within 3 years （56.5%） （x^2=4.361, P〈0.05）. The patients with poorer differentiation whole wall invasion, lymph node metastasis and more advanced TNM stage had a shorter survival than did those with better differentiation, more superficial invasion, no lymph node involvement and earlier TNM stage; and it was statistically significant （P〈0.05）. However, tumor size, macropathologic type, age and gender had no prognostic impact on ESC patients （P〉0.05）. Conclusion： P-gp and p27 expression levels had a clinical prognostic significance in ESC. It could provide a reference basis for selecting the chemotherapy projection. The tumor differentiation degree, depth of invasion, lymph node involvement and TNM stages all were correlated to ESC patients＇ survival.

Macrophage migration inhibitory factor regulates proliferation of gastric cancer cells via the PI3K/Akt pathway

AIM:To investigate the effects of macrophage migration inhibitory factor (MIF) on proliferation of human gastric cancer MGC-803 cells and expression of cyclin D1 and p27Kip1 in them,and further determine whether the effects are related to the PI3K/Akt signal transduction pathway. METHODS:Gastric cancer MGC-803 cells were cultured and then treated with 50 μg/L recombinant human MIF (rhMIF) with and without a PI3K inhibitor,LY294002 (25 μmol/L). MTT assay was used to detect the prolifer-ation of MGC-803 cells. Cell cycle was detected by flow cytometry. Expression of cyclin D1 and p27Kip1 mRNA was by reverse transcription-polymerase chain reaction. Protein expression of phosphorylated Akt (p-Akt),Akt,cyclin D1 and p27Kip1 was examined by immunocyto-chemistry and Western blotting. RESULTS:rhMIF signifi cantly stimulated the prolifera-tion of MGC-803 cells and cell cycle progression from G1 phase to S phase in a concentration-and time-de-pendent manner. After the MGC-803 cells were treated with rhMIF for 24 h,the expression of cyclin D1 was signifi cantly up-regulated compared with the cells not treated with rhMIF at both mRNA and protein levels(0.97 ± 0.02 vs 0.74 ± 0.01,P = 0.002; 0.98 ± 0.05 vs 0.69 ± 0.04,P = 0.003). The p27Kip1 was down-regulated but only statistically significant at the protein level. rhMIF significantly increased the expression of p-Akt,which reached the peak at 30 min,but did not affect the expression of Akt. However,LY294002 inhibited all the effects of rhMIF.CONCLUSION:Macrophage MIF increases the proliferation of gastric cancer cells,induces the expression of cyclin D1 at the transcriptional level and inhibits the expression of p27Kip1 at the post-transcriptional level via the PI3K/Akt pathway.