Figure 6. UM-SCC-1R xenograft tumor cell growth inhibition by liposomal CDF.
A. UM-SCC-1R cells isolated from 10μM (3.0 μg/mL) cisplatin treatment were implanted subcutaneously in nude mice (2 × 106 cells/mouse). One week after tumor implantation when tumor nodules were seen, liposome CDF (50 mg/kg, 1 mg for the 20 g mouse in a maximal volume of 100 μl in saline) or liposome control were injected 5 days a week for 4 weeks. At the end of 4 weeks mice received an i.p. injection of cisplatin (100 μl of 7.5 μg/mL in saline solution). Statistically significant tumor cell growth inhibition is observed in liposomal CDF treated mice (p<0.05). B. Representative tumors are shown indicating growth inhibition in liposomal CDF treated mice. C. Statistically significant decrease in CD44 expression is seen in liposomal CDF injected animals in comparison to untreated and liposome alone injected animals (Liposomal CDF T3 vs Liposome T2/Liposome T3 and Controls is p = 0.0065, Liposomal CDF T4 vs Liposome T2/Liposome T3 and Controls is p = 0.0013). Quantitative RT-PCR data represent average of 4 values. D. Proposed mechanism of cisplatin and curcumin mediated growth inhibition of cancer stem cells. Cisplatin (CDDP) induced senescence operates through p16 and p53 which could also result in the activation of transcription factors and development of CSCs by the senescence associated proteins (SAPs). HPV infection could attract macrophages for the removal of senescent cells. The HPV non expressing tumors lose their ability to attract macrophages leading to the development of chemo-radiation resistant CSCs. Curcumin through the inhibition of transcription factors could play a role downstream of SAPs for the growth inhibition of chemo-radiation resistant CSCs.