Effects And Mechanisms Of ATRA Plus Genistein On Proliferation, Apoptosis And VEGF Expression Of Lung Carcinoma Cell Line A549

It has been confirmed that ATRA (all-trans retinoic acid)had the effect of inhibiting tumor cells growth and induce their differentiation, which was favored by many researchers to try to utilize this quality, to prevent and therapy human lung cancer. However, recently in USA, two large trials on protecting high-risk group of lung cancer (smoker or asbestine contactor) with the use ofβ- carotene, the precursor of ATRA, have found that the high dose intake ofβ- carotine could not defend those people; On the contrary, there were higher risk of resulting in lung cancer[1]. There was the evidence that ATRA has the ability to stimulate the genetic transcription of VEGF(Vascular Endothelial Growth Factor)[2]. On the other hand, there are some disadvantages to prevent ATRA to be widely used in clinic, such as the higher active dosage, the major side reaction and the drug resistance of some tumor cells against ATRA. As natural tyrosine protein kinase (TPK)inhibitor, 5,7,4'- Genistein has been of interest of effecting as antitumor agent, and some researches indicated that Genistein has the ability to induce tumor cells differentiation and promote them to apoptosis in some range of dosage. But this effect is somehow inferior. So, it is very important to investigate how to reduce the dosage and lessen the side reaction of the antitumor drugs, at the same time to promote their effect to antitumor. Some scholars proposed that it is significant to search for the application of low dose and multi-drug combined methods[3]. In this study, we try to cut down the latent risk of ATRA, which may encourage the genetic transcription of VEGF and stimulate tumor vessel angiogenesis, by drawing assistance from drug combination; At the same time, we hope to enhance antitumor effect of ATRA and Genistein through drug combination. On this basis, we plan to work on the regulation of expression of apoptosis correlated genes such as Bcl-2 and Bax, and cell cycle associated molecules such as pRb,CDK4 and CyclinD1, and adhesion molecules such as ICAM-1 and MUC1, by drawing assistance from ATRA plus Genistein in treating human lung carcinoma cell line A549, and to approach the molecular mechanism...