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Basic Research Journal of Medicine and Clinical Sciences ISSN 2315-6864 Vol. 5(9): Pp 153-164 December 2016

Copyright© 2015 Basic Research Journals

International Scientific Indexing lSI Impact Factor (0.836)


Full Length Research Paper


All-trans retinoic acid in combination with cisplatin and paclitaxel enhances apoptosis and up-regulates retinoic acid receptors in lung adenocarcinoma cells


Norma Hernández-Pedro1,2, Benjamin Pineda2, Elizabeth Langley3, Marcela Lizano4, Aleli Salazar-Ramiro2, Roxana Magaña-Maldonado2, Julio Sotelo2 and Oscar Arrieta1,5,6


1Experimental Oncology Unit. Deparment of Basic Research, Instituto Nacional de Cancerología, Mexico City, Mexico.

2Neuroimmunology Unit, Instituto Nacional de Neurologia y Neurocirugia, Mexico City, Mexico.

3Hormone Regulated Cancer Lab, Department of Basic Research, Instituto Nacional de Cancerología, Mexico City, Mexico.

4Unidad de Investigación Biomédica en Cáncer. Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City.

5Department of Medical Oncology, Instituto Nacional de Cancerología, Mexico City, Mexico.

6Universidad Nacional Autónoma de México, Mexico City, Mexico.


*Corresponding author email: ogar@unam.mx


Received 27 October, 2016; Acceptance 14 November 2016; Published 03 January, 2017




Purpose: Loss of expression of retinoic acid receptors (RAR) results in lack of response to treatment and cancer progression. All-trans retinoic acid (ATRA) is a potential chemotherapeutic and chemopreventive agent with differentiation-inducing, anti-proliferative and pro-apoptotic effects that up-regulates retinoic acid receptors. The aim of this study was to asses a possible synergistic combination of ATRA with chemotherapy in terms of pro-apoptotic and anti-proliferative effects as well as on RAR expression in non-small cell lung cancer (NSCLC). Methods: The human lung cancer cell line H1666, was treated with ATRA, cisplatin (CIS) and paclitaxel (PACLI) at different combinations. We analyzed cell viability by the MTT assay while cell cycle and apoptosis were determined by flow cytometry. RAR and RXR expression was determined by RT-qPCR. Results: ATRA combined with CIS or PACLI inhibited cell growth showing a synergistic effect at 24 hours. All Paclitaxel combined treatments arrested cells in the G2-M phase whereas ATRA-CIS increased the sub G0 population. Furthermore, ATRA alone enhanced apoptosis, and this effect was greater when combining ATRA-CISPACLI. Additionally, ATRA in all combinations promoted up-regulation of RARα,β and γ. Conclusion: The addition of ATRA to CIS or PACLI enhanced their antitumor effect in lung cancer cells. This effect was more evident with the ATRA-PACLI combination.


Keywords: Non-small cell lung cancer, All-trans Retinoic Acid, Cisplatin, Paclitaxel, Retinoic Acid Receptors, Apoptosis, Cell Cycle.


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Basic Research Journal of Business Management and Accounts.


Basic Research Journal of Education Research and Review.

Basic Research Journal of Agricultural Science and Review.

Basic Research Journal of Social and Political Sciences.


J. Med. Clin. Sci.

Vol. 5 No 9

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