Table 1 Genetic and pharmacological inhibition of autophagy synergize with therapeutic agents in various malignancies

Chemotherapy

 B cell lymphomas

Mice

Cyclophosphamide

Chloroquine Hydroxychloroquine

ATG5 shRNA

Complete tumor regression and delayed tumor recurrence

[103]

 Brain cancer

AM38 and 794 cells

Vemurafenib, Vinblastine

Chloroquine

–

Improved tumor cell kill

[104]

 Esophageal squamous cell carcinoma (ESCC)

EC9706 cells

5-FU

LY294002 (LY)

–

Improved the sensitivity of cancer cells towards 5-FU

[105]

 Esophageal squamous cell carcinoma (ESCC)

EC9706 cells

Cisplatin

3-methyladenine

–

Enhanced cisplatin-induced cell death and cell cyle arrest

[106]

 Colorectal cancer

HT29

5FU

Chloroquine

–

Reduced proliferation and cell growth, potentiated cell cycle arrest

[107]

 Colorectal cancer

SW480 and SW620

Oxaliplatin

–

ATG5, ATG7, shRNA

Decreased cell viability and promoted chemotherapy efficacy

[108]

 Glioma

U373-MG cells

Temozolomide

Bafilomycin A1

–

Suppressed proliferation and induced apoptosis

[109]

 Lung cancer

A549 cells

Paclitaxel Cisplatin

3-methyladenine

–

Enhanced cytotoxic effect of chemotherapy and promoted apoptosis

[110]

 Lung cancer

A549 cells

Cisplatin

3-methyladenine

–

Inhibited proliferation, induced apoptosis and increased chemosensitivity

[111]

 Lung cancer

A549 cells, mice

Cisplatin

Chloroquine

–

Improved efficeincy o f chemotherapy and suppressed tumour growth, reduced percentage of cancer stem cells

[101]

 Myeloid leukemias

K562 cells

Daunorubicin

Chloroquine U0126

ATG5, ATG7, Beclin-1 siRNA

Promoted chemotherapy efficacy

[112]

 Ovarian cancer

3AO and SKOV3

Paclitaxel

Chloroquine

ATG5 shRNA

Decreased self-renewal ability of cancer stem cells

[95]

 Pancreatic cancer

Mice

Gemcitabine

Chloroquine

ATG5, ATG7, Beclin-1 shRNA

Suppress cancer stem cells activity, cancer cell growth and tumour formation

[113]

 Pancreatic cancer

PANC-1, BxPC-3

5FU, Gemcitabine

Chloroquine

–

Potentiated growth-inhibitory effects

[114]

 Renal cancer

ACHN-5968, UOK257 cells

Paclitaxel

3-methyladenine

Beclin 1 siRNA

Enhanced paclitaxel-mediated cytotoxicity and apoptosis

[115]

Other therapies

 B cell lymphomas

Mice

ER signalling inhibitor, Tamoxifen

Chloroquine Hydroxychloroquine

ATG5 shRNA

Complete tumor regression and delayed tumor recurrence

[103]

 Bladder cancer

J82 and T24 cells

AR signaling inhibitor, Enzalutamide

3-methyladenine Bafilomycin A1 Chloroquine

ATG5 shRNA

Triggered apoptosis and inhibited proliferation

[116]

 Bladder cancer

UMUC3 cells, mice

AR signaling inhibitor, Enzalutamide

Chloroquine

–

Impaired tumour growth and improved therapeutic sensitivity

[116]

 Bladder cancer

EJ and T24 cells, mouse

Radiation

Chloroquine

–

Promotes radiosensitivity and induced apoptosis

[117]

 Cervical carcinoma

HeLa cells

Photodynamic therapy, Photofrin

–

sgATG5

Enhanced apoptosis and protein carbonylation

[118]

 Colorectal cancer

SW480 cells

PI3K-mTOR inhibitor, NVP-BEZ235

3-methyladenine Chloroquine

–

Reduced cell viability and enhanced apoptosis

[119]

 Lung Cancer

A549, NCI-H1299, SKMES-1 cells

EGFR inhibitor, Gefitinib, erlotinib

Chloroquine

ATG5, ATG7 siRNA

Augmented growth inhibition

[120]

 Melanoma

A2058, C8161, SKMEL2, UACC903,

mTOR inhibitor, Temsirolimus

Hydroxychloroquine

–

Impaired cancer cell growth and increased cell death

[73]

 Oral squamous cell carcinomas

KB cells, mice

Cytokine, IL24

3-methyladenine

–

Promoted apoptosis, attenuated tumour growth

[121]

 Renal cell carcinoma

RCC4 cells, mice

mTOR inhibitor, Temsirolimus

Chloroquine

ATG7 shRNA

Improved antitumour activity

[122]

 Renal cell carcinoma

A498

mTOR inhibitor, Temsirolimus

Chloroquine

–

Enhanced cycotoxicity and apoptosis

[57]