Pair Name	Resveratrol, Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	MGMT	hsa4255
	Up-regulation	Expression	PIAS3	hsa10401
	Up-regulation	Expression	PTPN11	hsa5781
	Up-regulation	Expression	PTPN6	hsa5777
	Up-regulation	Expression	SOCS3	hsa9021
	Down-regulation	Expression	STAT3	hsa6774
In Vitro Model	A-172	Glioblastoma	Homo sapiens (Human)	CVCL_0131
	LN-428	Glioblastoma	Homo sapiens (Human)	CVCL_3959
Result	Res inhibited STAT3 signaling through modulation of PIAS3, SHP1, SHP2, and SOCS3, thereby attenuating tumor growth and increasing sensitivity to TMZ. Therefore, Res is an ideal candidate to be used in TMZ combined chemotherapy for GBM.

Pair Name	Resveratrol, Temozolomide
Disease Info	[ICD-11: 2F7Z]	Glioma		Investigative
Biological Phenomena	Inhibition-->Autophagy
Gene Regulation	Down-regulation	Expression	MAP1LC3B	hsa81631
	Down-regulation	Phosphorylation	MAPK1	hsa5594
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens (Human)	CVCL_0022
In Vivo Model	U87 MG cells in 0.1 ml MEM were subcutaneously (s.c.) injected into the right hind flank of the mice. Tumor sizes were measured with a caliper and were calculated as 1/2 × length × width2 in mm3. When the tumors grew to about 100 mm3, the tumor-bearing mice were randomly separated into treatment groups (n = 6/group).
Result	TMZ-induced ROS/ERK-mediated autophagy protected glioma cells from apoptosis, and the combination of resveratrol with TMZ could improve the efficacy of chemotherapy for brain tumors.

Pair Name	Resveratrol, Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BIRC5	hsa332
	Down-regulation	Activity	MGMT	hsa4255
	Down-regulation	Phosphorylation	STAT3	hsa6774
In Vitro Model	RG2	Malignant glioma	Rattus norvegicus (Rat)	CVCL_3581
	LN-18	Glioblastoma	Homo sapiens (Human)	CVCL_0392
	LN-428	Glioblastoma	Homo sapiens (Human)	CVCL_3959
Result	Our results demonstrated synergistic effects of Res/TMZ on RG-2 cells and their bilaterally sensitizing effects to LN-18 and LN-428 cells. Frequent upregulation of MGMT and activation of STAT3 are the unfavorable factors for the treatment of GBMs and they may be the potential targets of Res/TMZ therapy.

Pair Name	Resveratrol, Temozolomide
Disease Info	[ICD-11: 2F7Z]	Glioma		Investigative
Biological Phenomena	Induction-->ROS-dependent AMPK-TSC-mTOR signaling pathway
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	CASP3	hsa836
	Up-regulation	Expression	CASP7	hsa840
	Up-regulation	Expression	CASP9	hsa842
	Down-regulation	Expression	CCNB1	hsa891
	Down-regulation	Expression	CDKN1A	hsa1026
	Down-regulation	Expression	LRRC59	hsa55379
	Down-regulation	Activity	MAPK1	hsa5594
	Down-regulation	Activity	MAPK14	hsa1432
	Down-regulation	Activity	MAPK8	hsa5599
	Up-regulation	Phosphorylation	TP53	hsa7157
In Vitro Model	SHG-44	Astrocytoma	Homo sapiens (Human)	CVCL_6728
In Vivo Model	SHG44 cells (5×10⁵ cells per mouse) in 5 μL of Hanks’ solution were injected intracranially into the right caudate nucleus of 6‐ to 8‐week‐old female nude mice using a screw guide technique as described
Result	TMZ in combination with resveratrol remarkably increased reactive oxygen species (ROS) production, which serves as an upstream signal for AMP-activated protein kinase (AMPK) activation. Subsequently, activated AMPK inhibited mTOR signaling and downregulated antiapoptosis protein Bcl-2, which was contributed to the additive antiproliferation effects of combination treatment. In an orthotopic xenograft model of GBM, TMZ plus resveratrol treatment significantly reduced the volume of tumor, which was confirmed by decreased expression of Ki-67, a marker of proliferation index