ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of anti-EGFR monoclonal antibody on the chemosensitivity of human colon cancer cells and explore the possible molecular mechanism.</p><p><b>METHODS</b>The inhibitory effect of irinotecan (CPT-11), oxaliplatin (L-OHP) and fluorouracil (5-Fu), used alone or in combination with anti-EGFR monoclonal antibody, on the proliferation of LoVo cells in vitro was assessed by MTT assay. The expressions of PI3K and Akt protein in the treated cells were examined by Western blotting, and their mRNA expressions were detected by RT-PCR.</p><p><b>RESULTS</b>Both h-R3 and C-225 treatments significantly increased the chemosensitivity of LoVo cells to irinotecan and oxaliplatin. 5-Fu and h-R3 coadministered showed a synergistic effect on the cells, but 5-Fu and C-225 had an antagonistic action. Treatment with C-225 or h-R3 resulted in lowered expressions of PI3K and Akt in LoVo cells.</p><p><b>CONCLUSION</b>Anti-EGFR monoclonal antibody can increase the chemosensitivity of human colon cancer cells to most chemotherapeutic drugs, and such effect might be attributed to the blocking of PI3K/Akt signaling pathway by these antibodies.</p>
Subject(s)
Humans , Antibodies, Monoclonal, Humanized , Therapeutic Uses , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Cell Line, Tumor , Cetuximab , Colonic Neoplasms , Drug Therapy , Metabolism , Oncogene Protein v-akt , Metabolism , ErbB Receptors , Allergy and Immunology , Signal TransductionABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanism of photodynamic therapy (PDT) in nude mice bearing human esophageal cancer cell line Eca-109 xenografts.</p><p><b>METHODS</b>A nude mouse model bearing human esophageal carcinoma was established by subcutaneous transplantation of Eca-109 cells. The mice were then randomized into 4 groups, namely hematoporphyrin derivative (HpD)-PDT group (given HpD and laser irradiation), exclusive laser irradiation group, exclusive HpD group and blank control group. In HpD-PDT group, the mice were exposed to irradiation at the light energy density of 120 Jsol;cm(2) delivered via a DIOMED 630 PDT system 24 h after intraperitoneal HpD injection, and the mice in exclusive laser irradiation group received only laser irradiation. Three days later, all the nude mice were sacrificed for determination of malondialdehyde (MDA) production, immunohistochemistry for caspase-3 protein and HE staining of the tumor tissue.</p><p><b>RESULTS</b>The MDA level was significantly higher in HpD-PDT group than in the other 3 groups (P<0.01), and comparable between the latter 3 groups. Expression of caspase-3 protein was similar between HpD-PDT group and the blank control group (P>0.05). Under light microscope, HE staining visualized massive tissue necrosis in HpD-PDT group with homogeneous red staining.</p><p><b>CONCLUSION</b>In human esophageal carcinoma xenografts in nude mice, HpD-PDT generates singlet oxygen to result in direct tumor cell damage and cause MDA production. Caspase-3 may not be activated in the apoptotic pathway, suggesting that this pathway may not be caspase-3-dependent.</p>
Subject(s)
Animals , Female , Humans , Male , Mice , Cell Line, Tumor , Esophageal Neoplasms , Drug Therapy , Pathology , Hematoporphyrin Derivative , Therapeutic Uses , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Photochemotherapy , Random AllocationABSTRACT
Objective:To investigate the single nucleotide polymorphisms(SNP), haplotypes and genotypes of mannan-binding lectin(MBL) gene in the Bai(Pai) nationality from YunNan province, China.Methods:The three SNP sites CGT52TGT, GGC54GAC and GGA57GAA(named alleles D, B and C respectively, wildtype named A) in exon1 of MBL gene of 70 DNA samples of Bai nationality whose three SNP sites, -550G/C, -221C/G and +4C/T(named alleles H/L, X/Y and P/Q respectively), in promoter region of MBL gene had been clear, haplotypes and genotypes of MBL genes were detected and analyzed by sequence specific primer-polymerase chain reaction.Results:It was found that in Bais population, the frequency of alleles B was 0.100, there only were five haplotypes, HYPA, LXPA, LYQA, LYPA and LYPB, whose frequencies were 0.250, 0.107, 0.407, 0.135 and 0.100 respectively, the frequencies of several genotypes were LYPA/LYPA 0.043, LXPA/LYQA 0.143, LYPA/LYPB 0.014, HYPA/LYQA 0.086, LYPA/ LYQA 0.157, HYPA/LYPA 0.014, LYPB/LYQA 0.143, HYPA/LYPB 0.043, LXPA/LXPA 0.014, HYPA/LXPA 0.043, LYQA/LYQA 0.143 and HYPA/HYPA 0.157.Conclusion:In the MBL genes in Bais population, there is the allele B, the polymorphism haplotypes are mostly LYQA and HYPA, and the genotypes, LYPA/LYQA, HYPA/HYPA, LXPA/LYQA, LYPB/LYQA and LYQA/LYQA.