Figure 7. Autophagy inhibition with chloroquine increases the median event free survival of MDAMB231 but not MCF7 breast tumor xenografts and synergizes with chemotherapy primarily in autophagy dependent cells.
A) Female nu/nu mice were injected with 5 × 106 MDAMB231 or MCF7 cells into the 4th mammary fat pad. Upon reaching a tumor volume of 118 mm3 in MCF7 and 126 mm3 in MDAMB231, mice were treated with chloroquine (60 mg/kg/day) or 0.9% saline, intraperitoneally. Data is presented as time to reach 4-times initial volume (TV*4). Log-rank (Mantel-Cox) analysis of the curves shows significant difference for the MDAMB231 tumors and no significant difference for the MCF7 tumors. Tumor sections were stained for LC3 and pictures show a representative image. Bar represents 200 μM. B) MCF7, MDAMB231 and MDAMB468 cell lines were treated with doxorubicin (DOX) at different doses (μM) in combination with CQ (μM). Combination index (CI) was determined where log CI < 0 is synergistic, CI = 0 additive and CI > 0 is antagonistic. Graph shows one representative experiment of two independent experiments.