Figure 4.

Combination of ribociclib and alpelisib inhibit the growth of NPC patient-derived xenografts. (A) Representative PDX tumors at the end point of drug treatment. Tumor volumes in both xeno-666 and xeno-2117 were significantly reduced by the combination treatment. (B) Mice were administered with vehicle, ribociclib, alpelsilib and combination treatment by oral gavage. Combination treatment can significantly reduce tumor volume in xeno-666 (**p < 0.01, ribociclib vs combination at post-inoculation day 26) and xeno-2117 (**p < 0.01, ribociclib vs combined at post-inoculation day 58). (Fractional tumor volume = tumor volume/tumor volume before drug treatment) Values were presented as mean ± SEM (n = 10 to 12 per group for xeno-666, n = 7 to 11 per group for xeno-2117 at end point, note that some mice were euthanized when tumors exceeded maximum allowable size considering animal ethics) The body weights of mice between groups were comparable in both PDX models, indicating the drug combination was well-tolerated. (C) Western blots for the xenografts after drug treatments. Significant reduction of pRb expression was observed in ribociclib groups. Alpelisib co-treatment had significantly reduced the ribociclib induced pAKT level. (D) Representative immunohistochemical staining images from PDX tissue. Significant reduction of pRb expression but the obvious increase in cyclin D1 was observed in both PDX tumors after ribociclib treatment. PCNA staining was significantly reduced in co-treated tumors, suggesting a reduction of cancer cell proliferation. (scale bar = 100 µm).