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The Experimental Reseearch Of Polo-like Kinase 1 Expression In Gastric Carcinoma

Posted on:2007-03-01Degree:MasterType:Thesis
Country:ChinaCandidate:Q ZhangFull Text:PDF
GTID:2144360242463498Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
AIM: To study the expression of polo-like kinase 1 (PLK1) and its relationship with clinicopathological characteristics, anti-oncogene and tumor proliferation in human gastric carcinoma and to explore the role of PLK1 in the carcinogenesis and progression of tumor, and its clinical significance.METHODS: Expression of PLK1, P53 and Ki67 was detected in gastric carcinoma (n=54), atypical hyperplasia and normal gastric tissues (n=21, n=20) by the immunohistochemical method respectively.RESULTS: PLK1 was negatively expressed in all normal mucosa tissues. Weakly positive staining for PLK1 was observed in 5 out of 21 atypical hyperplasia tissues. The expression of PLK1 was elevated in 88.9% (48/54) of the gastric carcinoma. There were no significant associations between PLK1 and clinicopathological characteristics such as sex, age, histological differentiation, distant metastasis and lymph node metastasis (P>0.05). PLK1 expression was significantly related to the depth of invasion (χ2=6.775, P <0.01) and TMN stage (χ2=9.009, P <0.01).In gastric cancer, positive staining for P53 was detected in 38 of 54 cases (70.4%). P53 expression was significantly association with PLK1 (χ2=6.664, P <0.05). The mean value of Ki67 Labelling Index (Ki67 LI) was 34.7±13.4% (?X±s), with a range of 10.3%-60.1%. PLK1 expression was positively associated with Ki67 level (r=0.720,P <0.01).CONCLUSION: PLK1 was overexpressed in gastric cancer, and associated with tumor proliferation and anti-oncogene. PLK1 plays an important role in the carcinogenesis and development of gastric carcinoma, have potential as a new tumor marker and an attractive target of directed therapy for gastric carcinoma and estimate prognosis. AIM: To explore the role of PLK1 in carcinogenesis and development of gastric carcinoma and clinical significance for cancer therapy with the technique of RNAi (RNA interference).METHODS: SGC7901 cells were transfected with siRNAs (small interfering RNAs) targeted against the human PLK1 by chemosynthesis. The PLK1 mRNA levels of cells transfected with siRNAs were monitored by real time PCR and the protein levels were detected by immunocytochemistry. Cell proliferation was evaluated by direct cell counting with trypan blue staining. Cell cycle and apoptosis were examined by flow cytometry.RESULTS: The PLK1 mRNA levels of transfected gastric carcinoma cells had greatly decreased , as compared with the control groups which were 39.2±0.9% for 48h (P<0.01), and the protein levels also reduced. Cell proliferation was reduced from 24h after transfection. Cell cycle distribution was changed and showed a strong G2/M arrest which was 24.1±1.8%, about one fold compared to the controls at 48h after transfection, and 31.1±1.9% , about one and half fold compared to the control at 72h after transfection (P<0.01). Meanwhile, cell apoptosis was also increased, and the apoptosis rates were 12.3±2.3% and 35.9±2.6% respectively at 48h and 72h after transfection (P<0.01).CONCLUSIONS: PLK1 plays an important role in the carcinogenesis and development of gastric carcinoma. siRNAs targeted against human PLK1 may specially suppress the expression of PLK1 mRNA in gastric carcinoma cells, inhibit cell proliferation and enhance cell apoptosis . The use of RNAi targeting PLK1 will be potentially an effective guideline in gene therapy for human gastric cancer.
Keywords/Search Tags:Polo-like kinase 1, Gastric carcinoma, P53, Ki67, RNA interference, Real time PCR
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