Studies On The Correlation Between Pten,Livin Expression And Chemosensitivity Of Esophagfal Carcinoma

ObjectiveIn digestive systerm, esophgeal squamous cell cancer 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 esophageal tumor cells by using MTT and the protein expressions of PTEN and Livin in esophageal cancer tissues, and to explore the relationship between PTEN or Livin expression and chemosensitivity of esophageal cancer. We also determined whether these results can be used to help therapy the esophageal carcinoma.MethodsIn all,81 esophgeal squamous cell cancer 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 3×105 cells 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 Livin in esophageal cancer tissues were detected by immunohistochemistry (IHC).ResultsThe chemosensitivity of 81/84 cases were tested using MTT assay in esophgeal squamous cell cancer. The morphologic changes and decrease of metabolic activity of esophageal 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 38/81(47.5%) in normal cardia tissues and 20/20(100%) in esophageal carcinoma tissues (P<0.01). Expression of PTEN protein was significantly negatively related to that of Livin (rs=-0.678,P<0.01). A significantly lower tumor PTEN protein expression was associated with The degree of differentiation and lymph node metastasis of esophageal cancer (P<0.05), but no relationship with the depth of invasion(P>0.05). None of the normal tissues stained positive for Livin, wheres 56 of 81 (70%) esophageal carcinoma exhibit positive immunostaining for Livin (P<0.01). The Livin positive immunostaining of esophageal carcinoma was significantly related to The degree of differentiation and lymph node metastasis of esophageal cancer(P<0.05), but no relationship with the depth of invasion(P>0.05). The positively Livin stained cells showed resistance to 5-FU and ADM; Antitumor effects of HCPT,DDP,ADM and 5—FU were not correlated with The degree of differentiation and lymph node metastasis and depth of invasion of esophageal cancer(P>0.05).Conclusion1.Chemosensitivety testing of fresh human esophageal 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 Livin protein could be help to The degree of differentiation and lymph node metastasis of esophageal cancer;3. Expression of PTEN protein was significantly negatively related to that of Livin., This result approve that PTEN make the function of restraining cancerization by regulating nagetively the expression of Livin besides by its own action.4. The Livin positive cells showed resistance to 5-FU and ADM. Our results suggest that.Livin positive expression may contribute to primary drug-resistance of tumor.