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Objective To investigate the effect of cetuximab (C225) on the radiosensitivity of colorectal cancer cells CL187 and underlying mechanism.Methods Cell survival was detected by colony forming assay.The levels of apoptosis and cell cycle distribution were determined by flow cytometer.The mitotic ratio was measured by Wright' s-Giemsa mixed coloring method.The protein levels of Bax and Bcl2 were detected by Western blot.Results The sensitizing enhancement ratio of C225 was approximately 1.4.C225 treatment and 125I seed radiation induced G1 cell cycle arrest individually.C225 increased the radiation-induced apoptosis (t =6.6,P ＜ 0.05) and cellular Bax/Bcl-2 ratio (t =9.4,P ＜ 0.05),but did not increase radiation-induced G1 arrest.In addition,there was no difference in mitotic index among different groups.Conclusions C225 sensitizes CL187 to 125I seed irradiation,which might be related with increase of radiation-induced apoptosis.
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Objective To investigate the effect of C225 on DNA repair and molecular pathways in CL187 colorectal cancer cells after irradiated by 125Ⅰ radioactive seeds.Methods In the experiment involved were four groups:control group,100 nmol/L C225 treatment group,125Ⅰ radioactive seeds continuous low-dose rate irradiation group and C225 combined with 125Ⅰ radioactive seeds continuous lowdose rate irradiation group.Cells were collected at 48 h after 4 Gy irradiation,and γH2AX foci/cell and γH2AX foci positive cells were counted with immunofluorescence.At the same time,DNA repair proteins were detected by Western blot.Cells were lyzed immediately after 4 Gy irradiation,and changs in EGFR downstream signaling molecules were detected by Western blot.Results Compared with 125Ⅰ seeds irradiated cells,cells treated with C225 and 125Ⅰ seeds irradiation showed more γH2AX foci per cell (t =8.0,P =0.05),and more γH2AX foci positive cells (t =6.8,P ＜ 0.05) and less expression of Ku70 (t =6.6,P ＜ 0.05) and DNA-PKcs (t =5.6,P ＜ 0.05).Combined with 125Ⅰ-CLDR irradiation,C225 reduced cellular EGFR level(t =4.9,P ＜0.05) and inhibited the activation of Akt(t =5.5,P ＜0.05).Conclusions In the condition of 125Ⅰ seeds irradiation,C225 reduced the expression of Ku70 and DNA-PKcs,inhibited the activation of Akt and attenuated the DNA damage repair capacity in CL187 colorectal cancer cells.
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Objective To explore the inhibition effects of epidermal growth factor receptor (EGFR) antagonist monoclonal antibody cetuximab (C225) on breast cancer stem cells in human breast cancer cell line MCF-7.Methods The effects of C225 on the proliferation of breast cancer cell line MCF-7 were detected by MTT assay. MCF-7 cells were cultured to generate primary mammospheres, and were divided into control group, C225 group, epidermal growth factor (EGF) group and EGF + C225 group according to whether or not the culture media contained exogenous EGF and C225.Thirteen days after culture, the volume and number of mammospheres of these four groups were observed, and mammosphere-forming efficiency ( MFE) was calculated. The percentages of CD44~+ CD24~- cells in mammospheres of these four groups and in routinely cultured MCF-7 cells were determined by flow cytometry. Results The inhibition rate on MCF-7 cells increased with the concentration of C225.Compared with control group, the volume of mammospheres in C225 group significantly decreased, and MFE and percentages of CD44~+ CD24~- cells in mammospheres significantly decreased [(0.61 ±0.04)% vs (1.44±0.09)%, P<0.01; (3.50±0.29)% vs (9.07 ±0.52) % , P<0.01]. Compared with EGF group, the volume of mammospheres in EGF + C225 group significantly decreased, and MFE and percentages of CD44~+ CD24~- cells in mammospheres significantly decreased [ (0.68 ± 0.04) % vs (1.61 ± 0.05) % , P < 0.01; (4.00 ± 0.58) % vs (10.47 ± 0.79) % , P < 0.01]. The percentage of CD44~+ CD24~- cells in routinely cultured MCF-7 cells was (2.03 ±0.15) % , and was significantly different from those in EGF group and control group (P < 0.01). There was no significant difference in volume of mammospheres, MFE and percentage of CD44~+ CD24~- cells in mammospheres between EGF group and control group (P >0.05). Conclusion C225 has significant inhibition effects on CD44~+ CD24~- cells in MCF cells.
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Objective To evaluate the efficacy and safety of cetuximab(C225) with FOLFOX4 in the treatment of metastatic colorectal cancer (mCRC). Methods 68 patients with mCRC diagnosed by pathology were randomized in two groups: cetuximab combination with FOLFOX4 chemotherapy (combined group) and FOLFOX4 chemotherapy only (control group). Results The overall response rates (RR=CR+PR)in the combined group and the control group were 57.6 % and 32.3 % with significant difference (P <0.05). Grade Ⅲ/Ⅳ toxicity were myelosuppression(27.3 % and 32.4 %, P >0.05), nausea and vomiting(12.1% and 27.7 %, P >0.05), acne-like rash (only in combined group 9.1%). Conclusion The combination of cetuximab and chemotherapy can improve treatment efficacy. Except for rash, other grade Ⅲ/Ⅳ toxicity has no difference between the two groups.
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Objective:To investigate the modulating effects of anti-epidermal growth factor monoclonal antibody Cetux- imab(C225)on the ehemosensitivity and radiosensitivity in a Docetaxel-resistant human lung adenocarcinoma cell line SPC-A-1/doeetaxel.Methods:Radiosensitivity of SPC-A-1/docetaxel was determined by clone formation experiment and quantified by calculating the enhancement ratio(ER).The growth inhibition of SPC-A-1/docetaxel cell line caused by C225 or combination of C225 and Docetaxel in different orders was detected by MTT assay.The effect of C225 on cell cy- cle distribution and apoptosis was determined by flow cytometry.Results:C225 combined with radiation significantly de- creased the number of the cell clones than radiation alone;the D_0 values were 1.73 Gy for the former and 2.39 Gy for the latter,and the enhancement ratio was 1.38.C225 alone at concentration up to 1000?g/ml for 48h had neither cytotoxic nor eytostatie effect on SPC-A-1/docetaxel in vitro.C225 administration followed by Docetaxel significantly decreased the ICw of Docetaxel(85.2?g/ml vs 128.7?g/ml).Flow cytometry demonstrated that C225 exposure induced apoptosis of SPC-A-1/docetaxel cells in a time-dependent manner.The cell in the G_0/G_1 fraction increased from(43.80?4.46)% to (60.50?6.57)%(P
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The epidermal growth factor receptor (EGFR) provides a rational target for cancer therapy as it is commonly overexpressed in a variety of solid tumors, and its deregulation is correlated with resistance to chemotherapy and radiotherapy and a poor prognosis. Cetuximab (C255), a specific monoclonal antibody directed against EGFR, is synergistic with chemotherapy and radiotherapy and has been licensed for the treatment of irinotecan refractory colorectal cancer (CRC) and squamous cell cancer of the head and neck (SCCHN), which express EGFR. In addition, the clinical trials about cetuximab for the treatment of non-small cell lung cancer (NSCLC), breast and pancreas carcinoma are ongoing, and cetuximab has been proven to a novel strategy for the treatment of cancer with the overexpression of EGFR.