. 2016 Feb 2;35:23. doi: 10.1186/s13046-016-0303-5

Table 1.

In vitro studies of autophagy inhibiors on the TMZ anti-glioblastoma activity

Cell lines	Therapeutic methods (concentration /exprosure time)	Major findings	Interpretation	Reference
Rat C6 cells	TMZ 100–1,000 μM/24 hours	CQ potentiated TMZ-induced cytotoxicity.	CQ increaseed cellular ROS in glioma cells by inhibiting mitochondrial autophagy.	[35]
Human U87 cells	CQ 10 μM/24 hours	CQ potentiated TMZ-induced cytotoxicity.		[35]
Human LN229, U251 and U87 cells	TMZ 20–100 μM/48 hours	CQ increased the chemosensitivity of glioma cells to TMZ.	CQ blocked autophagy and triggered endoplasmic reticulum stress.	[48]
Human LN229, U251 and U87 cells	CQ 10-25 μM/48 hours	CQ increased the chemosensitivity of glioma cells to TMZ.		[48]
Human GBM8901cells	TMZ 100 μM/24 hours	Chrysin induced apoptosis, suppressed migration and invasion, and sensitized GBM cells to TMZ.	Chrysin inhibited TMZ-induced autophagy and MGMT expression.	[75]
Human GBM8901cells	Chrysin 20 μM/24 hours			[75]
Human U87, GBM8401 and GBM-SKH cells	TMZ 400 μM/72 hours	Resveratrol enhanced the therapeutic effect of TMZ against malignant glioma.	Coadministration of resveratrol and TMZ reduced tumor volumes by suppressing ROS/ERK-mediated autophagy.	[42]
Human U87, GBM8401 and GBM-SKH cells	Resveratrol 10 μM/1 hours			[42]
Human U87, U251 and SHG‑44U87 cells	TMZ 100 μM/72 hours	ATM inhibitor ku-55933 enhanced TMZ cytotoxicity in inherently TMZ‑sensitive glioma cells.	Ku-55933 inhibited the phosphorylation of AMPK, and reduced the levels of TMZ-induced autophagy.	[54]
Human U87, U251 and SHG‑44U87 cells	Ku-55933 10 μM/72 hours			[54]
Human U87 and U251 cells	TMZ 100 μM/72 hours	TMZ chemoresistance was overwhelmed by targeting ATM.	Ku‑55933 inhibited the activation of ULK1 and interrupted the cytoprotective process of autophagy.	[55]
Human U87 and U251 cells	Ku-55933 10 μM/72 hours	TMZ chemoresistance was overwhelmed by targeting ATM.		[55]
Human U-118 cells	TMZ 0–500 μM/24-48 hours	Inhibition of ERK1/2 partially eradicated the chemoresistance of U-118 GBM cells to TMZ.	ERK1/2 specific inhibitors U-0126 prevented the activation of autophagy by TMZ.	[19]
Human U-118 cells	U-0126 15 mM/48 hours			[19]
Human U87 cells	TMZ 400 μM/0–72 hours SP600125 10 μM/1 hours	TMZ-induced autophagy is mediated by JNK activation.	JNK inhibitor suppressed TMZ-induced JNK phosphorylation, further blocked autophagy and increased apoptosis.	[61]
Human LN229 and U251 cells	TMZ 100 μM/24 hours	Targeting eEF-2 kinase can enhance the anti-glioma activity of TMZ.	Inhibition of eEF-2 kinase by SiRNA or NH125 blocked the activation of TMZ-induced autophagy.	[65]
	eEF-2 SiRNA N/A
	NH125 0.5 μM/24 hours
Human U251 cells	TMZ 200 and 400 μM/72 hours	Inhibition of autophagy potentiated the cytotoxicity of curcumin or TMZ as well as TMZ/curcumin combination.	Autophagy inhibition sensitizes TMZ and curcumin treated cells to apoptosis.	[81]
	Curcumin 15 μM/72 hours
	3-MA 4 mM/72 hours
Human U87 cells	TMZ 400 μM/36-72 hours	TMZ induced autophagy through mitochondrial damage- and ER stress-dependent mechanisms to protect glioma cells.	ETC inhibitors rotenone, sodium azide, oligomycin, or ER stress inhibitor 4-PBA reduced autophagy and consequently increased TMZ-induced apoptosis.	[61]
	rotenone 20 nM/1 hour
	sodium azide 150 μM/1 hour
	oligomycin 1 nM/1 hour
	4-PBA 10mM/1 hour
Human U87 and U251 cells	TMZ 50–200 μM/48 hours	Targeting VAMP8 alleviated TMZ resistance in glioma cells.	silencing of VAMP8 by SiRNA could impaire the TMZ-induced autophagic flux.	[69]
Human U87 and U251 cells	VAMP8 SiRNA N/A	Targeting VAMP8 alleviated TMZ resistance in glioma cells.		[69]