Bevacizumab and CCR2 Inhibitor Nanoparticles Induce Cytotoxicity-Mediated Apoptosis in Doxorubicin-Treated Hepatic and Non-Small Lung Cancer Cells

Abstract

Non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC) are very common in certain population<br />around the world. Despite the recent advances in their diagnosis and therapy, their prognosis remains poor due to the<br />development resistance to drug. Although doxorubicin (DOX) is considered to be one of the most anti-solid tumor<br />drugs, developed resistance is contributing to unsuccessful outcome. The rationale of the current study is to explore<br />the sensitizing capability of the DOX-treated cancer cells using the anticancer agents; bevacizumab (avastin; AV) and<br />CCR2 inhibitor (CR) in their free- and nano-formulations. Here, the average size, polydispersity index (PDI), zeta<br />potential, and entrpment effeciency (EE%) of the synthesized nanoparticles were measured. We investigated the effect<br />of these platforms on the proliferation, apoptosis, necrosis, nitric oxide (NO), malondialdehyde (MDA), and zinc levels<br />of human HCC (HepG2 and Huh-7) and NSCLC (A549) cancer cell lines. Glucose consumption rates using Huh-7<br />and A549 cancer cells were tested upon treatments. We demonstrated that AV and CR nano-treatments significantly<br />suppressed A549 cell viability and activated apoptosis by NO level elevation. We concluded that AVCR NP plus<br />DOX significantly induces A549 cytotoxicity-mediated apoptosis more than Huh-7 and HepG2 cells. This drug-drug<br />nano-combination induced Huh-7 cytotoxicity-mediated apoptosis more than HepG2 cells. In conclusion, AVCR NP<br />sensitized DOX-treated A549 and Huh-7 cells through reactive oxygen species (ROS)-stimulated apoptosis. Taken<br />together, our data suggested that the CR plus AV nano-platforms would be a potential personalized medicine-based<br />strategy for treating CCR2-positive NSCLC and HCC patients in the near future.