Figure 9.

CQ selectively accelerated cell death in Akti-treated PTEN-null cells in vitro and enhanced the antitumor efficacy of Akt KD in vivo. (A) PTEN−/− (−/−) MEFs were more sensitive than isogenic PTEN+/+ (+/+) counterparts to the combined treatment with Akti-1/2 and CQ. MEFs were treated with 5 μM each of Akti-1/2 and CQ under 1% FBS, and cell viability was determined at days 0, 2, and 3 by PI exclusion. Error bars represent SEM (n = 3). (B) Mean tumor volumes of PC3 xenograft tumors treated daily with vehicle (Veh), Dox only, CQ only, or both Dox and CQ over a 28-d period. The vehicle and vehicle + CQ groups were followed for up to 18 d before terminated because of weight loss from the tumor burdens. Error bars represent SEM (n = 10 tumors in each cohort). (C) Scatterplot of the tumor volumes in the Dox only and Dox + CQ groups on day 28 (P = 0.05). Horizontal bars indicate mean tumor volumes. Numbers of tumors with complete remission (CR, dashed line) are indicated for each group. (D) Individual tumor growth plotted as a percentage of tumor volume change compared with day 0 for the Dox only and Dox + CQ cohorts shown in B. Dashed lines indicate −100% change from the starting tumor volumes, i.e., complete tumor regression. Numbers of tumors with smaller (<0% change) or larger (>0% change) than the starting tumor volumes on day 28 are indicated.

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