Table 5.

Summary of related research on NCTD overcoming multidrug resistance

Cancers	Cell lines	Basic mechanisms	Pathways	Accompanying roles	Experiment	References
Oral cancer	SAS, Ca9-22	Activation of caspase-9, enhancing Bax, downregulating Bcl-2, Bcl-XL			In vitro	[108]
Breast cancer	MCF-7S, MCF-7R, MDA-MB-231, BT-474		Inhibiting Shh signaling and expression of its downstream mdr-1/P-gp expression		In vitro	[103]
	MDA-MB-231, MDA-MB-468, MDA-MB-415, AU565	Inhibiting SMAC mimetic Birinapant-mediated cell viability and promoting apoptosis and cell death; reducing c-FLIP; enhancing Birinapant-triggered caspase-8/caspase-3, Inhibiting caspase-8	Downregulation of c-FLIP	With SMAC mimetics promoting Birinapant-mediated anticancer activity		[172]
Hepatocellular cancer	Multiple HCC cell lines	Inducing transcriptional repression of Mcl-1 and enhancing ABT-737-mediated cell viability inhibition and apoptosis; activation of mitochondrial apoptosis pathway, involving cytosolic release of cytochrome c, cleavage of caspase-9, -3	Enhancing ABT-737-induced apoptosis by transcriptional repression of Mcl-1	Enhancing ABT-737 therapeutic efficacy	In vitro	[111]
	HepG2, SMMC-7721	ABT-737 plus NCTD have stronger proliferation inhibition, greater apoptosis induce and stronger Mcl-1 inhibiting, thus enhancing the release of cytochrome C and ABT-737 inducing apoptosis		With ABT-737 solving resistance of ABT-737 to liver cancer		[112]
Neuroblastoma	SH-SY5Y CHLA-119	Enhancing ABT-263-mediated apoptosis, inhibiting cell viability and clonal formation; upregulating Noxa with cytosolic release of cytochrome c, activation of caspase-9, -3, and cleavage of PARP	Enhancing ABT-263-mediated anticancer activity by upregulation of Noxa		In vitro	[113]
Hepatocellular cancer; Cervical cancer	HepG2 Hela	Inhibiting PTX-induced Cdc6 up-regulation, maintaining Cdk1 activity, and repressing Cohesin/Rad21 cleavage, thus reducing mitotic slippage and overcoming PTX resistance	Reducing mitotic slippage and overcoming PTX resistance via inhibiting Cdc6		In vitro	[155]
Pancreatic cancer	PANC-1, CFPAC-1	Repressing cell growth and stemness marker CD44, CD24, EPCAM, CD44(+)/CD24(+)/EPCAM(+) proportion, and β-catenin pathway-dependent manner; strengthening the cytotoxicity of gemcitabine and erlotinib	Repressing the stemness of pancreatic cancer cells through repressing β-catenin pathway, strengthening the cytotoxicity of gemcitabine, erlotinib	Strengthening the cytotoxicity of gemcitabine, erlotinib	In vitro	[173]
NSCLC	PC-9 HCC827	Reversing resistance to EGFR-TKIs induced by exogenous and endogenous HGF in EGFR mutant lung cancer cells via inhibiting the Met/PI3K/Akt pathway; NCTD plus gefitinib regressing tumor growth and Akt phosphory in vivo	Inhibition of Met/PI3k/Akt pathway	With EGFR-TKIs in vitro, with gefitinib in vivo	In vitro In vivo	[116]
Lymphoma	Multiple myeloma cells	Induction of G2/M arrest; down-regulating IKKα and p-IκBα	Inactivation of NF-kB signaling pathway	Enhancing bortezomib- antimyeloma activity	In vitro In vivo	[174]