Abstract 5385: Thymoquinone(TQ) and cisplatin(CDDP) in a non-small cell lung cancer (NSCLC) xenograft model

Abstract

Abstract Introduction: Lung cancer is the leading cause of cancer related death in United States. The most active chemotherapeutic agent for NSCLC is Cisplatin. Thymoquinone (TQ) is the bioactive constituent of the volatile oil of The Black Caraway seed also known as (Nigella Sativa, Ranunculaceae family) and has been shown to have anti-neoplastic activities. Based on our intvitro data we combined CDDP and TQ in a mouse xenograft model using NSCLC cell line NCI-H460. Materials and Methods: a) Cisplatin at 2.5mg/kg was prepared weekly by dissolving in PBS. Cisplatin was injected i.p. once a week for three weeks. b) TQ was prepared in concentrations 5mg/kg or 20mg/kg and dissolved in solvent of cremophor: alcohol: PBS in a ratio (1:1:4) and injected subcutaneous M, W, F for 3 weeks. These doses were selected based on an earlier Maximum tolerated dose (MTD) study. 5-6 weeks old female SCID mice were obtained from harlan laboratories and were placed under pathogen free conditions in animal care facility according to LSU, Shreveport animal care guidelines. Animal protocol was reviewed and approved by animal care committee. NCI-H460 2×10^6 cells were injected subcutaneous into right flank after shaving that area. Tumors were allowed to grow for one week and when tumor volume reached approximately 20mm3 mice were randomized to 6 groups with 10 mice in each group. Tumor volume was calculated using the formula V= (LxW2) x 0.5 where V= volume, L= length, W=width. c) Treatment groups: Mice were randomized into following 6 groups (n=60) treated as described above for 3 weeks. 1) Control 2) TQ 5mg/kg s.c. M,W,F 3) TQ 20mg/kg s.c. M,W,F 4) Cisplatin 2.5mg/kg i.p. Monday 5) Combination (1): Cis2.5mg/kg/TQ5mg/kg 6) Combination (2): Cis 2.5mg/kg/TQ20mg/kg. Tumor volume and body weight was measured M, W, F for three weeks during the course of study. At (Day 26) mice were sacrificed and tissue samples were obtained for histological analysis Statistical analysis: For statistical analysis we used factorial analysis of variance (ANOVA) and a p value of < 0.05 taken as significant. Results: Results show that TQ alone at 5mg/kg s.c. M,W, F had no effect on reducing tumor volume in fact mean tumor volume was higher as compared to control but not statistically significant. TQ alone at 20mg/kg was active and reduced tumor volume (p 0.075). Cisplatin alone at 2.5mg/kg reduced tumor volume significantly (p <.0001). This effect was seen in combination arms too with significant inhibition of tumor volume by combination of TQ at 5mg/kg and 20mg/kg along with CDDP (p value of 0.036 and 0.0016) In the combination arm (TQ5mg/kg/Cis 2.5mg/kg) tumor volume was reduced by 59% and (TQ20mg/kg /Cis 2.5mg/kg) tumor volume was reduced T.V by 79% as compared to control. Conclusion: TQ alone and in combination with CDDP significantly reduces tumor volume in a NSCLC mouse xenograft model and should be considered for future clinical development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5385.