Induction of apoptosis in A549 human lung cancer cells by all-trans retinoic acid incorporated in DOTAP/cholesterol liposomes
Induction of apoptosis in A549 human lung cancer cells by all-trans retinoic acid incorporated in DOTAP/cholesterol liposomes
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DOI：
10.1016/j.jconrel.2005.10.030
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发表时间：
2006-02-21
影响因子：
10.8
通讯作者：
Hashida, M
中科院分区：
文献类型：
--
作者：
Kawakami, S;Suzuki, S;Hashida, M
全反式维甲酸（ATRA）已被证明在许多类型的癌细胞中发挥抗癌活性。然而，据报道，许多非小细胞肺癌表现出耐药性的ATRA治疗。在本研究中，我们假设ATRA的细胞内递送将克服ATRA在A549细胞中的抗性。在这里，我们研究了诱导凋亡的ATRA纳入阳离子脂质体组成的DOTAP/胆固醇在A549人肺癌细胞，这是不敏感（耐）ATRA的生长抑制作用。DOTAP/胆固醇脂质体和DSPC/胆固醇脂质体的zeta电位约为+50和-3 mV。在A549细胞中，与[H-3]ATRA或[H-3]ATRA掺入DSPC/胆固醇脂质体相比，[H-3] ATRA掺入DOTAP脂质体显示出增加的细胞缔合。ATRA掺入DOTAP/胆固醇脂质体显示出更高的细胞毒作用和诱导凋亡活性与ATRA或ATRA掺入DSPC/胆固醇脂质体相比。ATRA掺入DOTAP/胆固醇脂质体后，TIG 3 mRNA表达增强，这可能部分解释了ATRA增强DOTAP/胆固醇脂质体细胞毒性和/或细胞凋亡的机制。这些观察结果提供了有价值的信息，以帮助设计分化治疗的ATRA在非小细胞肺癌。(C)2005 Elsevier B. V.保留所有权利。
All-trans retinoic acid (ATRA) has been shown to exert anti-cancer activities in a number of types of cancer cells. However, it has been reported that many NSCLC exhibited resistance to ATRA treatment. In the present study, we hypothesized that intracellular delivery of ATRA would overcome the ATRA resistance in A549 cells. Here, we investigated the induction of apoptosis by ATRA incorporated in cationic liposomes composed of DOTAP/cholesterol in A549 human lung cancer cells, which are insensitive (resistant) to the growth inhibitory effects of ATRA. The zeta potentials of DOTAP/cholesterol liposomes and DSPC/cholesterol liposomes were about +50 and -3 mV. In A549 cells, [H-3]ATRA incorporated in DOTAP liposomes showed increased cellular association compared with [H-3]ATRA or [H-3]ATRA incorporated in DSPC/cholesterol liposomes. ATRA incorporated in DOTAP/cholesterol liposomes showed much higher cytotoxic effects and apoptosis-inducing activity compared with ATRA or ATRA incorporated in DSPC/cholesterol liposomes. The enhanced expression of TIG3 mRNA tumor suppressor gene by ATRA incorporation into DOTAP/cholesterol liposomes might partly explain the mechanism of enhanced cytotoxicity and/or apoptosis. These observations provide valuable information to help in the design of differentiation therapy by ATRA in non-small cell lung carcinoma. (C) 2005 Elsevier B.V. All rights reserved.