“Lung cancer is the major cause of cancer-related mortality worldwide.Many of these over-express epidermal growth factor receptor(EGFR), and are usually highly aggressive and resistant to chemotherapy.
Recent studies have shown that -9 Tetrahydrocannabinol (THC),the major component of Cannabis sativa, possess anti-tumor propertiesagainst various types of cancers.
However, not much is knownabout its effect on lung cancer. In this study, we sought tocharacterize the effect of THC on EGF-induced growth and metastasisof human non small lung cancer cell (NSCLC) lines A549 and SW-1573.
We demonstrate that these cell lines and primary tumor samplesderived from lung cancer patients express cannabinoids receptorsCB1 and CB2, the known targets for THC action. We further showthat THC inhibits EGF-induced growth in these cell lines. Inaddition THC attenuated EGF-stimulated chemotaxis and chemoinvasion.Next we characterized the effect of THC on in vivo lung cancergrowth and metastasis in a murine model. A549 cells were implantedin SCID mice (n=6 per group) through subcutaneous and intravenousinjections to generate subcutaneous and lung metastatic cancer,respectively. THC (5mg/kg body wt.) was administered once dailythrough intraperitoneal injections for 21 days. The mice wereanalyzed for tumor growth and lung metastasis.
A significantreduction (~50%) in tumor weight and volume were observed inTHC treated animals compared to the vehicle treated animals.THC treated animals also showed a significant (~60%) reductionin macroscopic lesions on the lung surface in comparison tovehicle treated control. Immunohistochemical analysis of thetumor samples from THC treated animals revealed anti-proliferativeand anti-angiogenic effects of THC with significant reductionin staining for Ki67, a proliferative marker and CD31, an endothelialmarker indicative of vascularization. Investigation into thesignaling events associated with reduced EGF-induced functionaleffects revealed that THC also inhibits EGF-induced Akt phosphorylation.Akt is a central signaling molecule of EGFR-mediated signalingpathways and it regulates a diverse array of cellular functions,including proliferation, angiogenesis, invasion and apoptosis.
Cumulatively, these studies indicate that THC has anti-tumorigenic and anti-metastatic effects against lung cancer. Novel therapies against EGFR overexpressing, aggressive and chemotherapy resistant lung cancers may include targeting the cannabinoids receptors.”