Table 4 In vitro studies of autophagy inducers on the TMZ anti-glioblastoma activity
From: Targeting autophagy to sensitive glioma to temozolomide treatment
Cell lines | Therapeutic methods (concentration /exprosure time) | Major findings | Interpretation | Reference |
|---|---|---|---|---|
Human U87/EGFR and U251 cells | TMZ 5 and 50μM/48-72 hours dasatinib 200 nM/48-72 hours | Augmentation of Dasatinib-Induced Autophagy in combination with Temozolomide. | TKI increased autophagic cell death and sensitivity of TMZ therapy. | [93] |
Human T98G and U373 cells | TMZ (300 μM) was added to the culture immediately after IR/ time: N/A rapamycin 0.1, 0.5, and 1 mM/24 hours | Autophagy-associated cell death sensiyized glioma cells to combined radiotherapy/ TMZ treatments. | Rapamycin-mediated autophagy promoted malignant glioma cell death induction after combined radiotherapy/TMZ treatments. | [23] |
Human U251, U87, and T98G cells | TMZ 25 μM/24 hours IR 6Gy/6 hours PI103 0.4 μM/24 hours | A dual inhibitor of class I PI3K/mTOR, PI103, increased the cytotoxic effect of radiation therapy plus TMZ. | Enhanced radiosensitizing effects of TMZ by PI103 induced the autophagy and apoptosis, and reversed the EMT. | [100] |
Human NCH82 cells | TMZ 500 μM/72 hours SKI 10 μM/72 hours | SKI could sensitize GBM cells to TMZ treatment. | Combination of TMZ and SKI resulted in autophagic flux increased and further induction of cell death potentiation. | [105] |
Human T98G and SF295 cells | TMZ 25μM/96 hours VPA 1mM/96 hours | VPA increased the sensitivity of glioma cells to TMZ. | VPA enhanced the activities of TMZ on glioma cells through blocking cell cycle and promoting autophagy. | [109] |
Human U87, U343, LNT-229, and MZ-54 cells | TMZ100μM/96 hours (−)-Gossypol 15μM/48 hours | Pan-Bcl-2 inhibitors augmented the action of TMZ on apoptosis-resistant malignant glioma cells. | Pan-Bcl-2 inhibitors (−)-Gossypol induced caspase-independent, autophagic cell death when combined treatment with TMZ. | [112] |
Human T98G and U373 cells | TMZ 100μM/48 hours EGFR SiRNA 1μM/72 hours | EGFR interfering resulted in an increase of TMZ cytotoxicity in TMZ-resistant GBM cells. | EGFR SiRNA inhibited the pro-death autophagy and sensitized GBM cells to subsequent TMZ treatments | [97] |
Human U251 cells | TMZ 100 μM/72 hours Nrf2 shRNA N/A | Combination of TMZ and the knockdown of Nrf2 could enhance the antitumor effects of TMZ in GBM. | Knockdown of Nrf2 by shRNA enhanced autophagy induced by TMZ. | [117] |
Human U87, T98G, and HG19 cells | TMZ 25-75μM/72 hours THC 0.9μM/72 hours | Coadministration of TMZ with THC exerted a strong antitumoral action in glioma cells. | Combined administration of THC and TMZ enhanced autophagy-mediated apoptosis in tumor cells. | [86] |
Human T98G and U251 cells | TMZ 300-500 μM/24 hours WA 0.5-2μM/24 hours | Combination treatment with WA and TMZ resulted in resensitization of TMZ-resistance | Withaferin A resensitizes TMZ-resistant GBM cells to TMZ through MGMT depletion | [87] |
Human U87 and U373 cells | TMZ 100 μM/24 hours oncolytic adenovirus 100 vp per cell/24 hours | Oncolytic adenovirus led to improved efficacy of TMZ treatment against a panel of glioma cell lines. | Combination of oncolytic adenovirus with TMZ increased tumor cell autophagy and apoptosis-mediated cell death. | [90] |
Rat RG2 cells | TMZ 100 μM/48 hours PTx 20 ng/ml /48 hours | PTx has the potential to be useful as an adjunct to TMZ chemotherapy on glioma. | Concomitant treatment with TMZ and PTx elicited autophagic cell death in vitro and increased the survival in RG2 glioma model. | [122] |