Basic studies on chemoprevention for head and neck cancer

众所周知，全反式维甲酸（ATRA）对急性早幼粒细胞白血病（APL）细胞具有分化作用，ATRA是治疗APL的有效药物。类维生素a在头颈部癌前病变化学预防中的作用已被报道。晚期头颈癌病例的预后很差，尽管有治愈性治疗，即放射治疗和/或手术配合化疗和/或免疫治疗。因此，对于晚期头颈部肿瘤，一种新的治疗方式是必不可少的。研究了细胞分化相关药物vesnarinone、pamidronate二钠、ATRA以及维生素D3衍生物22-oxacalcitriol （OCT）和1alpha， 25(OH)2D3对人头颈部鳞状细胞癌细胞DNA合成的抑制作用。并比较治疗组与未治疗组肿瘤细胞对化疗药物的敏感性及形态变化。各药物治疗后，肿瘤细胞的生长均受到不同浓度药物的抑制。在维生素D3衍生物中，OCT对DNA合成的抑制作用强于1alpha， 25(OH)2D3。在比较OCT和/或ATRA对细胞生长的抑制作用时，联合治疗对DNA合成的抑制作用最强。在细胞周期检查中，处理导致G0-G1期细胞增多，S期细胞减少。在CDDP或5-FU的敏感性试验中，ATRA或vesnarinone治疗后CDDP的IC50显著降低。经处理的肿瘤细胞对表皮生长因子的反应较弱。此外，显微镜下观察OCT和/或ATRA处理后的形态学变化。处理后的细胞变大，树突延伸。这些发现提示细胞分化相关药物在头颈部人类鳞状细胞癌治疗模式中的潜在有用性。少

It is well known that all-trans retinoic acid (ATRA) differentiate acute promyelocytic leukemia (APL) cells and ATRA is an efficacious drug for APL.The usefullness of retinoids in chemoprevention for premalignant lesions in the head and neck has been reported. The outcome of cases with advanced head and neck carcinomas is poor in spite of curative treatments, i.e., radiation therapy and/or surgery with chemotherapy and/or immunotherapy. Therefore, a new treatment modality is indispensable for advanced head and neck carcinimas.The inhibitive effects of cell differetiation-related agents, vesnarinone, pamidronate disodium, ATRA and derivatives of Vitamin D3, i.e., 22-oxacalcitriol (OCT) and 1alpha, 25(OH)2D3, on DNA synthesis of human head and neck squamous cell carcinoma cell lines were examined. Futhermore, the sensitivity against chemotherapeutic drugs and morphologocal changes of treated tumor cells was compared to that of non-treated ones. After the treatment with each drug, the cel … More l growth of treated tumor cells was inhibited dependetly on the concentration of each treatment drug. In the derivatives of Vitamin D3, OCT showd a stronger suppression on DNA synthesis than 1alpha, 25(OH)2D3 did. In terms of the comparison of suppressive effects on cell growth between the treatment with OCT and/or ATRA,the combined treatment represented the strongest suppression of DNA synthesis. In cell cycle examination, the treatment resulted in a increase of cells in G0-G1, with an accompanying decrease of cells in S phase. With regard to sensitivity tests using of CDDP or 5-FU,IC50 for CDDP decreased markedly after the treatment with ATRA or vesnarinone. The treated tumor cells showed a less responsiveness to epidermal growth factor. In addition, morphological changes were observed by microscopic analysis after OCT and/or ATRA treatment. The treated cells became bigger and extended the dendrites.These findings suggest the potential usefulness of cell differentiation-related drugs in treatment modality for human squamous cell carcinomas of the head and neck. Less