Fig. 6. Tumor growth associated with HPV16 E2/E4/E5 expression is inhibited by FGFR inhibitor AZD4547 alone and in combination with mTOR inhibitor rapamycin.
a AZD4547 synergizes with rapamycin in inhibiting cell viability of four HPV positive cancer cells. Four HPV positive cancer cell lines were treated with different concentration of AZD4547 (from 0 to 10,000 nM) and rapamycin (from 0 to 300 nM) at the same time. After 3 days, the viability was measured and growth inhibition was calculated normalized by the untreated cells (0 nM AZD4547, 0 nM rapamycin). b Growth inhibition histogram on the left and RT-qPCR on the right. Growth inhibition was measured at 3 days after treated with AZD4547 (1 uM), or/and rapamycin (200 nM), and normalized by the first day. Right histogram shows the expression of HPV16 E2, E4, E5, E6 and E7 in four HPV positive cancer cell lines. Data represent mean ± SEM. P values were calculated using two-sided Student t test. *P < 0.05; **P < 0.01; ***P < 0.001. c Western blot results of UD-SCC-2 cells after treated with AZD4547 or/and rapamycin for 3 days. AZD4547 induced decrease in pFGFR1, FGFR1, pFGFR3, FGFR3, pFRS2 and pAKTT308, and synergized with rapamycin in decrease in pFGFR1, FGFR1, pFGFR3, FGFR3, pFRS2, FRS2, pAKTT308 and pS6.