[Expression features of P-glycoprotein, glutathione S transferase-pi and inhibitor of apoptosis proteins in lymph node metastases of gastrointestinal carcinomas].

OBJECTIVE: To investigate the expression features of P-glycoprotein (P-gp), glutathione S transferase-pi (GST-pi) and inhibitor of apoptosis proteins like p53, survivin and bcl-2 in lymph node metastases of gastrointestinal carcinomas. METHODS: The expression of P-gp, GST-pi, p53, survivin and bcl-2 were determined by using immunohistochemistry technique in surgical specimens of primary tumor (PT) and lymph node metastases (LNMs) from 54 gastrointestinal cancer patients with metastasis of lymph nodes. The expression difference of 5 multi-drug resistance (MDR)-related factors between LNMs and PT were compared. RESULTS: Significant difference was found in the expression of P-gp and GST-pi between the two groups (both P < 0.05), and expression of p53 and bcl-2 showed positive correlation between LNMs and PT (r = 0.7248, 0.5524; both P < 0.05), respectively. In LNMs, P-gp expression was positively correlated with GST-pi (r = 0.4062, P < 0.05) and survivin (r = 0.6169, P < 0.05), and also GST-pi expression was related positively with survivin (r = 0.4027, P < 0.05). Statistically positive correlations were noted between bcl-2 and P-gp (r = 0.3986, P < 0.05), bcl-2 and survivin (r = 0.2937, P < 0.05), as well as GST-pi and survivin (r = 0.4481, P < 0.01) in PT. Only a positive correlation between GST-pi and survivin expression was simultaneously shown in both LNMs and PT. CONCLUSIONS: There is significant heterogeneity of MDR-related factors expression in LNMs of gastrointestinal carcinomas. Effective adjuvant chemotherapy after operation should target on the metastatic loci of the disease.

[Correlation of expression of P-glycoprotein and inhibitor of apoptosis proteins to chemosensitivity in gastrointestinal carcinoma tissues].

BACKGROUND & OBJECTIVE: P-glycoprotein (P-gp) mediated classical drug resistance and inhibition of the apoptotic pathway are the two mostly investigated mechanisms of multidrug resistance (MDR). Coexpression and interaction of MDR-related factors result in pleiotropic drug resistance in cancer cells. This study was to investigate the correlation of expressions of multiple MDR-related factors, such as P-gp, p53, Survivin or bcl-2, to chemosensitivitity in gastrointestinal carcinomas. METHODS: Eighty-four tissue specimens of gastrointestinal carcinomas were analyzed. Expressions of P-gp, p53, Survivin and bcl-2 were determined by immunohistochemistry (IHC). Drug chemosensitivity of nine drugs to cancer cells were measured by MTT assay. RESULTS: The positive staining of P-gp, p53, Survivin and bcl-2 were detected in 96.4%, 64.3%, 89.3% and 60.7% of all specimens, respectively. The expression of P-gp and bcl-2 (r=0.5072, P<0.05), and the expression of survivin and bcl-2 (r=0.3027, P<0.05) were positively correlated. The inhibition rates of paclitaxel (PTX), oxaliplatin (OXA) or cisplatin (DDP) on cancer cells were significantly lower in the group with strong P-gp expression than that with weak P-gp expression (all P<0.05). The strong expression of p53 was correlated with decreased inhibition rates of PTX and DDP on cancer cells (P<0.05, P<0.01). When the expression of Survivin was increased, the inhibition rates of vincristine (VCR) or DDP on cancer cells were reduced significantly (P<0.05, P<0.01), but the inhibitory effect of OXA was remarkably increased (P<0.01). The inhibition rates of 5-fluorouracil (5-FU), VCR, epirubicin (EADM) and OXA on cancer cells were lower in the group with strong expression of bcl-2 than in that with weak expression of bcl-2 (P<0.05). CONCLUSIONS: The expression of MDR-related factors in gastrointestinal carcinomas is associated with drug resistance of only certain chemotherapy drugs. Multiple factors and mechanisms should be considered when assessing the influence of MDR related factors on drug resistance.