[Relationship of cyclooxygenase-2 and multidrug resistance associated factors to chemosensitivities in gastrointestinal carcinomas].
OBJECTIVE
To investigate the relationship of cyclooxygenase-2 (COX-2), p-glycoprotein(P-gp), glutathione S-transferase-pi (GST-pi), and topoisomerase II alpha (Topo II alpha) to chemosensitivities in gastrointestinal tract carcinomas.


METHODS
The tumor tissue samples were collected from 84 specimens of gastrointestinal carcinomas. The expressions of COX-2, P-gp, GST-pi, and Topo II alpha were determined immunohistochemically. The chemosenisitivity of each sample to 9 drugs were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.


RESULTS
The positive rates of COX-2, P-gp, GST-pi and Topo II alpha were 48.8%, 76.2%, 78.6% and 66.7% respectively. The expression of COX-2 was correlated with the expression of P-gp and Topo II alpha significantly (r = 0.287, 0.256, both P < 0.05). In terms of relationships of four MDR-related factors expression to inhibition rate of tumor cells, the inhibition rates of PTX, eADM and OPT in COX-2 strong expression group were significantly lower than those in COX-2 weak expression group (t = 2.21, 3.11, 2.09; all P < 0.05). The inhibition rates of PTX, OXA and DDP in P-gp strong expression group were lower than those in weak group (t = 2.54, 2.47, 2.05; all P < 0.05). There were lower inhibition rates for 5-Fu in GST-pi strong expression group (t = 2.13, P < 0.05), and higher inhibition rates for VCR, PTX and eADM in TopoII alpha strong expression group (t = -2.29, -2.12, - 2.26, all P < 0.05).


CONCLUSIONS
The overexpressions of MDR-related factors in gastrointestinal carcinomas were only associated with the chemosensitivity to some of the chemotherapeutic agents, but not all. MDR related factors may be not specific and accurate predictors for the clinical chemosensitivity.
Tan
Bi-Bo
BB
Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, China.
Li
Yong
Y
Han
Jie
J
Fan
Li-Qiao
LQ
Zhao
Qun
Q
Song
Zhen-Chuan
ZC
Wang
Dong
D
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D004250:DNA Topoisomerases, Type II