Some of them have been tested in the clinic. However, a large proportion of existing VEGF-targeted agents selleck products were found to have modest efficacy, when used singly in treatment of various cancers except for certain specific types of malignancy. They have thus mainly been used in combination with chemotherapy or radiotherapy. An example of this is bevacizumab (Avastin), a humanized monoclonal antibody to VEGF, which is only of benefit for patients with NSCLC when combined with conventional chemotherapy [9]. Investigations are underway with the aim of

exploring more effective ways of administering and combining anti-VEGF agents with chemotherapeutic drugs. Chemotherapy has dominated systemic therapy of cancer for a long time. In the setting of metastatic disease, chemotherapy used to be the only available approach. For NSCLC, DDP-based regimen remains the mainstay of chemotherapeutic treatment of patients with either resected or locally advanced or, metastatic diseases [2, 10]. DDP-based regimens often cause severe toxic side effects, including myelosuppression, asthenia and gastrointestinal disorder, as well as long-term www.selleckchem.com/products/pexidartinib-plx3397.html cardiac, renal and neurological consequences. These adverse events usually cause drug discontinuation, poor tolerance and limited therapeutic efficacy [11, 12]. Preclinical and clinical

studies are in progress to test various dosing/scheduling strategies

for chemotherapy to increase efficacy and decrease toxicity. Thus far, most existing VEGF-targeted agents belong to the category of recombinant protein. However, RNAi technology has been proven to be a promising alternative approach for targeted therapy and various RNAi tools are under intensive investigation. In this study, we investigated a novel strategy of administering and combining RNAi mediated VEGF-targeted therapy with DDP for treatment of lung cancer. Methods Construction of shRNA expressing plasmid A plasmid-based shRNA expression system was used to endogenously express shRNA in human cancer cells. The targeted sequence of human VEGF: 5′-AAA CCU CAC CAA GGC CAG CAC-3′ this website (21 nt) was selected according to a previous study [13]. The control sequence which was named HK: 5′-GAC TTC ATA AGG CGC ATG C-3′ (19 nt) had no homology to any mammalian sequence. Recent evidence has revealed that U6 promoter is greatly superior to the other promoters in driving plasmid based shRNA expression and pU6shRNA is at least 100-fold more potent in gene silencing than corresponding siRNA on a numerical basis [14]. Thus, we elected U6 promoter to control the recombinant plasmids which were constructed and prepared as described elsewhere [15]. The resulting plasmids were named pshVEGF and pshHK, respectively.