Studies On The Correlation Between PTEN,Survivin Expression And Chemosensitivity Of Gastric Carcinoma

Objective:In digestive systerm, gastric carcinoma is one of the most common maligmant tumour, which was treated mainly by operation, companied by chemotherapy. But chemotherapy does not produce desired effects that contribute to the differrent chemosensitivity of individual patients and clinical empirical application for patients. Therefore, we conducted the present study to evaluate the chemosensitivity of primary culturing gastric tumor cells by using MTT and the protein expressions of PTEN and survivin in gastric cancer tissues, and to explore the relationship between PTEN or survivin expression and chemosensitivity of gastric cancer. We also determined whether these results can be used to help therapy the gastric carcinoma.Methods: In all, 84 gastric carcinoma fresh specimens from surgically resected tsssues were obtained. And then tissues were excised from serosa side and the rim of tumor without necrosis and degeneration. A single-cell suspension of tumor cells (2×105 to 3×105cells ml-1)were separately exposed to Hydroxycamptothecin (HCPT), cisplatin (CDDP),5-fluorouracil (5-FU),adriamycin (ADM),mitomycin (MMC) at ten times peak plasm concentrantion (PPC) Inhibitory rate of cells was detected by MTT assay. Expression of PTEN and survivin in gastric cancer tissues were detected by immunohistochemistry (IHC).Results: The chemosensitivity of 80/84 cases were tested using MTT assay in gastric cancer. The morphologic changes and decrease of metabolic activity of gastric cancer cells were observed after exposure to antitumor drugs. The results showed that the sensitivity of MMC,5-FU and HCPT was significantly higher than CDDP and ADM(P<0.05); In the later,the sensitivity of CDDP was significantly higher than ADM(P<0.01); The positive expression of PTEN was 38/80 (47.5% ) in normal cardia tissues and 20/20(100% ) in gastric carcinoma tissues (P<0.01). Expression of PTEN protein was significantly negatively related to that of survivin (rs=-0.678,P<0.01). A significantly lower tumor PTEN protein expression was associated with the differentiation pathologic grade of gastric cancer, TNM stage and lymph node metastasis of gastric cancer (P<0.05), but no relationship with the depth of invasion(P>0.05). None of the normal tissues stained positive for survivin, wheres 56 of 80 (70%) gastric carcinoma exhibit positive immunostaining for survivin (P<0.01). The survivin positive immunostaining of gastric carcinoma was significantly related to the differentiation pathologic grade of gastric cancer, TNM stage and lymph node metastasis of gastric cancer(P<0.05), but no relationship with the depth of invasion(P>0.05). The positively survivin stained cells showed resistance to 5-FU and ADM; Antitumor effects of HCPT,DDP,ADM and 5-FU were closely related to the differentiation pathological grade of gastric cancer(P<0.05), but not correlated with TNM stage and lymph node metastasis and depth of invasion of gastric cancer(P>0.05). Conclusion: 1.Chemosensitivety testing of fresh human gastric cancer using MTT assay could constitute the prediction on applying chemo-drugs and identify drug-resisting cases.2. Over expressions of PTEN protein and low expressions of survivin protein could be help to the TNM stage and lymph node metastasis of gastric cancer;3. Expression of PTEN protein was significantly negatively related to that of survivin., This result approve that PTEN make the function of restraining cancerization by regulating nagetively the expression of survivin besides by its own action.4. The survivin positive cells showed resistance to 5-FU and ADM. Our results suggest that.survivin positive expression may contribute to primary drug-resistance of tumor.