Pemetrexed Induces G1 Phase Arrest and Apoptosis through Inhibiting Akt in Human A549 Non Small Cell Lung Cancer Cells

As the leading cause of cancer death worldwide, lung cancer has the highest incidence and mortality among 27 kinds of cancers (Ferlay et al., 2010). And non small lung cancer (NSCLC) has a proportion of 80%-85% in all lung cancers (Stinchcombe et al., 2009; Yu Z et al., 2014). In the firstand second-line treatment of non small lung cancer, chemotherapy is one of the common methods using chemotherapeutics drugs, such as pemetrexed and docetaxel (Bareschino et al., 2011; Gettinger et al., 2011). Pemetrexed (Alimta®) is an antifolate agent with a structure containing a core group of pyrrolo pyrimidine and inhibits the key enzymes (thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase) which are necessary for the synthesis of folic acid, thereby can block biological resynthesis process of thymine nucleotides and purine nucleotides. Pemetrexed is firstly used for treatment of malignant pleural mesothelioma combined with cisplatin. On August 19, 2004, FDA gave official approval for pemetrexed for injection in treatment with local advanced or metastatic non small lung cancer (Cohen et al., 2005). And up to now, pemetrexed has demonstrated antitumor activity