Table 5 Summary of related research on NCTD overcoming multidrug resistance

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]