Zou C P, Kurie J M, Lotan D, Zou C C, Hong W K, Lotan R
Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Clin Cancer Res. 1998 May;4(5):1345-55.
Most human non-small cell lung cancer (NSCLC) cell lines are refractory to all-trans-retinoic acid (ATRA). Recently, N-(4-hydroxyphenyl)retinamide (4HPR) was found to induce apoptosis in various tumor cells. In this study, we compared and contrasted the effects of 4HPR and ATRA on the growth and apoptosis of 10 NSCLC cell lines and normal human bronchial epithelial (NHBE) cells. All of the cancer cell lines and the NHBE cells were sensitive to 10 microM 4HPR, and their numbers decreased to <20% of the controls after a 5-day treatment, whereas ATRA decreased cell numbers to about 50% of the controls in three cell lines and was less effective in the rest of the tumor cell lines. ATRA inhibited the growth of the NHBE cells by 70-80%. 4HPR induced apoptosis in most of the cells, including the ATRA-resistant ones, as evidenced by a DNA fragmentation assay. No correlation was found between growth inhibition by 4HPR and the expression of retinoic acid receptor beta (determined by Northern blotting and PCR), p53, or Bcl-2 proteins (analyzed by Western blotting). These results demonstrate that 4HPR is more potent than ATRA in inducing apoptosis in NSCLC cells and suggest that further clinical trials for prevention and therapy of NSCLC using 4HPR are warranted.
大多数人类非小细胞肺癌（NSCLC）细胞系对全反式维甲酸（ATRA）具有耐药性。最近，发现N-（4-羟基苯基）视黄酰胺（4HPR）可诱导多种肿瘤细胞凋亡。在本研究中，我们比较了4HPR和ATRA对10种NSCLC细胞系及正常人支气管上皮（NHBE）细胞生长和凋亡的影响。所有癌细胞系和NHBE细胞对10μM的4HPR均敏感，经5天处理后，细胞数量降至对照组的<20%，而ATRA使3种细胞系的细胞数量降至对照组的约50%，对其余肿瘤细胞系的作用较小。ATRA抑制NHBE细胞生长达70 - 80%。DNA片段化分析表明，4HPR可诱导大多数细胞凋亡，包括对ATRA耐药的细胞。未发现4HPR的生长抑制作用与视黄酸受体β（通过Northern印迹法和PCR测定）、p53或Bcl-2蛋白（通过Western印迹法分析）的表达之间存在相关性。这些结果表明，4HPR在诱导NSCLC细胞凋亡方面比ATRA更有效，提示有必要进一步开展使用4HPR预防和治疗NSCLC的临床试验。
