[Correlation of expression of P-glycoprotein and inhibitor of apoptosis proteins to chemosensitivity in gastrointestinal carcinoma tissues].
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.
Han
Jie
J
Department of Gastrointestinal Surgery, Hebei Provincial People's Hospital, Shijiazhuang, Hebei, China. hanjie01@yahoo.com.cn
Tan
Bi-Bo
BB
Geng
Wei
W
Lu
Bing-Rong
BR
Zhao
Jian-Hui
JH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D055815:Young Adult
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D016159:Tumor Suppressor Protein p53