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. 2020 Sep 16;25(11):2012–2022. doi: 10.1016/j.drudis.2020.09.010

Table 1.

Summary of in vitro and in vivo studies combining anticancer agents with CQ

Tumor type Intervention Intervention dose CQ dose Cell line/animal model Therapeutic effect Refs
APL Arsenic trioxide 1 μM 10, 25 uM NB4 Suppressing cell growth, inhibiting autophagy, and inducing mitochondrial pathway apoptosis and S phase arrest [90]

BC Trichostatin A 0.5 μM 25 μM MCF10A, MCF10A-ras Inducing cell apoptosis by activating FOXO1 and inhibiting mTOR pathway [91]

CSCC Gefitinib 5 μM 50, 100 μM A431 Inhibiting protective autophagy and enhancing apoptosis [92]

GC Tenovin-6 0.2, 0.5, 1, 2, 4 μM 25, 50 μM AGSEBV, SNU-719, AGS, HGC-27, N87, SNU-1, KATO-III Inhibiting cell proliferation, inhibiting autophagy flux, and inducing G1 arrest and apoptosis with p53 activation [93]

GC CMG002 100 nM 10 μM AGS, NUGC3 Inducing apoptotic cell death by blocking PI3K/AKT/mTOR pathway [94]

HCC Doxorubicin 1 mg/kg 2 times/week 25 mg/kg/day Sprague–Dawley rats Inducing apoptosis by upregulating TRAIL/TRAILR2, caspase-3, and caspase-8 and downregulating Bcl-2 [95]

Hypophysoma Cabergoline 100 μM 20 μM GH3, MMQ Increasing cell death, enhancing disruption of autophagy; inducing apoptosis with accumulation of p62/caspase8/LC3-II [103]
0.5 mg/kg/2 days 50 mg/kg/day Athymic nude mice, F344 rats Suppressing tumor growth

Melanoma Temozolomide 100 μM 20 μM Mel MTP, Mel Z and Mel IL Potentiating TMZ-induced apoptosis, inducing G0/G1 arrest and enhancing cytotoxicity [96]

NEN Everolimus (RAD001) 3 mg/kg/day 60 mg/kg/day BON1 subcutaneous neoplasm mice Reducing tumor size and weight, inhibiting autophagy and increasing apoptosis with mTORC1 signaling pathway inhibition [97]

NPC Cisplatin 50 μM 5, 50 μM C666-1 Inhibiting cell viability and promoting apoptosis with high-expression of Beclin 1 and LC3B-II [98]

NSCLC Paclitaxel 10 nM 10 μM A549 Inhibiting tumor metastasis, reverting paclitaxel resistance and suppressing autophagy via ROS-mediated modulation of AKT activity and downregulation of Wnt/β-catenin pathway [99]
C2-ceramide 10, 20, 50 μM 10 μM H460, H1299 Inducing cytotoxicity, promoting cell apoptosis, inhibiting autophagy through inhibition of Src and SIRT1 and activation of LAMP2 and LC3-I/II [104]
5 μM 5 μM Zebrafish xenografts Inhibiting tumor growth
Honokiol 10, 20, 30, 40, 60 μM 10, 20 μM A549, H460 Inhibiting cell proliferation and inducing cell death in caspase-dependent and cathepsin D-involved manner [105]
50 mg/kg/day 100 mg/kg/day BALB/c nude mice Reducing tumor growth
Gefitinib 100 nM 10, 20 μM PC-9/wt, PC-9/gefB4 and PC-9/gefE3 Inducing apoptosis, inhibiting autophagy and reversing gefitinib resistance [106]
50 mg/kg/day 75 mg/kg/day BALB/c nude mice Potentiating gefitinib-induced antitumor activity and reducing tumor growth

OC Cisplatin 5 μM 5, 10 μM SKOV3, hey Inhibiting cell growth, migration, and invasion, inhibiting autophagy [107]
5 mg/kg/6 days 60 mg/kg/day BALB/c nude mice Reducing tumor volume and tumor weight

PC Gambogic acid 1, 2 μM 40 μM PANC-1, BxPC-3 Inhibiting autophagy by reducing mitochondrial membrane potential and increasing ROS accumulation [108]
8 mg/kg/3 days 100 mg/kg first day BALB/c nude mice Inhibiting tumor growth

RCC ABT-737 1 μM 25 μM A498, 786-O Decreasing cell viability, inducing lysosome-dependent cell death by increasing cellular ROS level [100]
Everolimus 15 μM 20 μM A498, RXF393, SN12C, 769P Inducing cell viability and apoptosis via intrinsic mitochondrial apoptotic pathway activation [101]

TNBC Osimertinib 2.4, 4, 6.5 μM 10, 30, 75 μM MDA-MB-231 Improving effectiveness of osimertinib through autophagy-apoptosis crosstalk pathway (pAKT inhibition and pBad activation) [102]
Isorhamnetin 10 μM 20 μM MDA-MB-231, MCF-7, BT549, MCF-10A Inhibiting cell proliferation, inducing apoptosis, inducing generation of ROS and inducing mitochondrial fission through phosphorylation of Camk II and Drp1 as well as their mitochondrial translocation [109]
20 mg/kg/2 days 40 mg/kg/2 days Nude mice Suppressing tumor growth

Abbreviations: APL, acute promyelocytic leukemia; BC, breast cancer; CSCC, cutaneous squamous cell carcinoma; GC, gastric cancer; HCC, hepatocellular; Int., interventions; NEN, neuroendocrine neoplasms; NPC, nasopharyngeal carcinoma; NSCLC, nonsmall cell lung cancer; OC, ovarian cancer; PC, pancreatic cancer; RCC, renal cell carcinoma; TNBC, triple-negative breast cancer.