목 적: 대장암 세포에서 epidermal growth factor receptor (EGFR) 저해제인 nimotuzumab에 의한 방사선 민감도 증진 효과를 살펴보고자 한다. 대상 및 방법: 총 4종류의 인간 유래 대장암 세포주인 HCT-8, LoVo, WiDr, HCT-116를 nimotuzumab과 방사선을 병합 처리한 후 세포증식, 생존율, 세포주기 진행에 미치는 영향을 MTT, clonogenic survival assay, flow cytometry와 western blot을 통해 분석하였다. 결 과: 대장암 세포주에서 nimotuzumab에 의해 EGFR 인산화가 억제됨을 확인하였고 이러한 조건에서 nimotuzumab이 HCT-116을 제외한 나머지 3종류의 대장암 세포주의 방사선 민감도를 증진시킴을 확인하였다. 반면에, nimotuzumab은 방사선 조사와 무관하게 대장암 세포의 증식이나 세포 주기에는 아무런 영향을 미치지 않았다. 결 론: Nimotuzumab은 EGFR에 의한 세포 생존 신호 전달을 억제함으로써 대장암 세포의 방사선에 대한 민감도를 증가시켰다. 본 연구는 대장암의 방사선 치료에 EGFR 특이적 저해제인 nimotuzumab의 임상 적용 근거를 제공하였다.
목 적: 대장암 세포에서 epidermal growth factor receptor (EGFR) 저해제인 nimotuzumab에 의한 방사선 민감도 증진 효과를 살펴보고자 한다. 대상 및 방법: 총 4종류의 인간 유래 대장암 세포주인 HCT-8, LoVo, WiDr, HCT-116를 nimotuzumab과 방사선을 병합 처리한 후 세포증식, 생존율, 세포주기 진행에 미치는 영향을 MTT, clonogenic survival assay, flow cytometry와 western blot을 통해 분석하였다. 결 과: 대장암 세포주에서 nimotuzumab에 의해 EGFR 인산화가 억제됨을 확인하였고 이러한 조건에서 nimotuzumab이 HCT-116을 제외한 나머지 3종류의 대장암 세포주의 방사선 민감도를 증진시킴을 확인하였다. 반면에, nimotuzumab은 방사선 조사와 무관하게 대장암 세포의 증식이나 세포 주기에는 아무런 영향을 미치지 않았다. 결 론: Nimotuzumab은 EGFR에 의한 세포 생존 신호 전달을 억제함으로써 대장암 세포의 방사선에 대한 민감도를 증가시켰다. 본 연구는 대장암의 방사선 치료에 EGFR 특이적 저해제인 nimotuzumab의 임상 적용 근거를 제공하였다.
Purpose: To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Materials and Methods: Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/o...
Purpose: To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Materials and Methods: Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. Results: An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Conclusion: Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.
Purpose: To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Materials and Methods: Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. Results: An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Conclusion: Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.
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제안 방법
Under the selected experimental condition, the combined effect on cell proliferation was then assessed using the MTT assay 48 hours after exposure to nimotuzumab, radiation, or both. As shown in Fig.
*2" t0 better understand the mfluence of the EGFR blockade on radiation response in colorectal cancer, we investigated the antitumor effect of combined treatment with nimotuzumab and radiation in colorectal cancer cell lines. In this study, nimotuzumab inhibited EGF- induced phosphorylation of EGFR and Akt in colorectal cancer cell lines (Fig. IB) and significantly enhance radiosensitivity when combined with radiation in most of colorectal cancer cell lines (Fig. 4). Interestingly, clonogenic survival assay 옹howed that nimotuzumab enhanced radiosensitivity of WiDr cell which was resistant to cetuximab treatment.
대상 데이터
To evaluate the combination effect of nimotuzumab and radiation, four human EGFR expressing colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were selected. First, the optimal dose of radiation was determined that caused approximately 20% growth inhibition of each type of colorectal cancer cells using MTT assay.
이론/모형
Cells were treated with nimotuzumab (500 nM) for 4 hours prior to irradiation. After 48 hours, cell proliferation was analyzed using the MTT assay. All treated cells were normalized to respective untreated controls.
성능/효과
Hone어!y Significant Differences Test and independent-sample t-test with SPSS ver. 12.0 (SPSS Inc., Chicago, IL, USA) and p-values <0.05 were accepted as statistically significant.
First, the optimal dose of radiation was determined that caused approximately 20% growth inhibition of each type of colorectal cancer cells using MTT assay. Therefore suitable radiation dose of each cell line was determined as 6 Gy for WiDr and 4 Gy for HCT-116 and 2 Gy for LoVo and HCT-8 (Fig.
was performed. Statistical analysis of survival curves re作화led that the cytotoxic effect of radiation on HCT-8, LoVo, and WiDr cells was enhanced significantly, with dose enhancement factors of 1.33, 1.67, and 1.86, respectively (p< 0.05) (Fig. 4). However, different from results of the other cell lines, treatment with nimotuzumab had no effect on radiation sensitivity of HCT-116 cells, with a dose enhancement factor of 0, 83.
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