Zhang W G, Li X W, Ma L P, Wang S W, Yang H Y, Zhang Z Y
Institute of Biophysics, Academia Sinica, Beijing, People's Republic of China.
Cancer Lett. 1999 Apr 26;138(1-2):189-95. doi: 10.1016/s0304-3835(99)00013-0.
To better understand the effects of p53 on the process of photodynamic therapy (PDT)-induced cell death, we introduced a wild-type p53 gene into the HT29 colorectal carcinoma cell line, which bears an endogenous mutant p53, using a lipofectin system. The influence of p53 status on the sensitivity induced by 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA) photosensitization was then examined. The results indicate that infection with wild-type p53 induces a growth arrest but does not induce cell death, and sensitizes the cells to PDT. At a concentration of 5 microM 2-BA-2-DMHA with a red light of 18 J/cm2 (lambda = 600-700 nm), the survival is reduced from 58.72% in HT29 cells to 13.49% in wild-type p53-infected HT29 cells. Apoptosis following PDT appears earlier in HT29 cells infected with wild-type p53 than in parent HT29 cells and empty vector-infected HT29 cells. These findings suggest that although wild-type p53 is, by itself, insufficient to induce apoptosis in cells with p53 mutation, it enhances the photosensitivity of 2-BA-2-DMHA by strongly potentiating the induction of apoptosis.
为了更好地理解p53对光动力疗法（PDT）诱导的细胞死亡过程的影响，我们使用脂质体转染系统将野生型p53基因导入携带内源性突变p53的HT29结肠癌细胞系中。然后检测p53状态对2-丁基氨基-2-去甲氧基竹红菌素A（2-BA-2-DMHA）光致敏诱导的敏感性的影响。结果表明，野生型p53感染可导致生长停滞，但不会诱导细胞死亡，并且使细胞对PDT敏感。在5 microM 2-BA-2-DMHA浓度和18 J/cm2红光（波长= 600 - 700 nm）条件下，HT29细胞的存活率从58.72%降至野生型p53感染的HT29细胞中的13.49%。PDT后的凋亡在野生型p53感染的HT29细胞中比在亲本HT29细胞和空载体感染的HT29细胞中出现得更早。这些发现表明，虽然野生型p53本身不足以诱导p53突变细胞凋亡，但它通过强烈增强凋亡诱导作用来提高2-BA-2-DMHA的光敏性。
