Combining Nelfinavir With Chloroquine Inhibits In Vivo Growth of Human Lung Cancer Xenograft Tumors

JACLYN LOPICCOLO; SHIGERU KAWABATA; JOELL J. GILLS; PHILLIP A. DENNIS

doi:10.21873/invivo.12241

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Figure 1.
Combining nelfinavir (NFV) with chloroquine (CQ) enhances inhibition of non-small cell lung cancer (NSCLC) proliferation and proteotoxicity. A: Growth inhibition by nelfinavir (■), chloroquine (▲), and their combination (●). H157 and A549 cells were treated with drugs at the indicated concentrations for 48 h. Data are the mean±SD. B: Enhancement of proteotoxicity. H157 and A549 NSCLC cells were treated with either dimethyl sulfoxide (DMSO), 10 μM nelfinavir, 80 μM chloroquine, or their combination for the indicated times. Immunoblotting analysis was performed for markers of proteotoxicity, endoplasmic reticulum stress, apoptosis, and autophagy.
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Figure 2.
Combining nelfinavir (NFV) with chloroquine (CQ) inhibits tumor growth of non-small cell lung cancer (NSCLC) in vivo. A: Tumor growth of H157 (upper panel) and A549 (lower panel) NSCLC cells as xenografts in athymic NCr-nu/nu. Data are the mean±SD. B: Representative photographs of two different mice bearing A549 xenograft tumors from each group after treatment for 13 days. Circles indicate tumors. C: Apoptosis and endoplasmic reticulum stress markers in vivo. The indicated markers were evaluated in the tumors using immunoblotting analysis as described in the Materials and Methods. V: Vehicle, N+C: nelfinavir + chloroquine. Data are the mean±SD of five mice. Significantly different at *p<0.05 and **p<0.01 compared with vehicle treatment.