Role of hypoxia in cancer therapy by regulating the tumor microenvironment

Table 1 Overview of HIF-1-mediated mechanisms in drug resistance

Resistance phenotype	Cancer/Cell type	Resistant chemotherapy drug	Molecular basis	Reference
Overexpression of drug efflux proteins	Colon cancer cells	5-Fluorouracil	MDR1/P-gp	[26]
Overexpression of drug efflux proteins	Ovarian carcinoma cells	Estramustine	ABCA2	[27]
Overexpression of drug efflux proteins	Lung adenocarcinoma cells	Adriamycin	P-gp	[28]
Apoptosis inhibition	Breast cancer cells	Paclitaxel	Caspases 3, 8, 10, and Bak	[29]
Apoptosis inhibition	Colon cancer cells	Etoposide and oxaliplatin	Bid and Bax	[30]
Apoptosis inhibition	Gastric cancer cells	5-Fluorouracil and cisplatin	p53 and NF-kB	[31]
Apoptosis inhibition	Human melanoma cells	Not mentioned	P53 and TRP2	[88]
Autophagy induction	HeLa cells	N-(4-Hydroxypheny) retinamide (4-HPR)	Beclin1	[32]
Autophagy induction	Gastric cancer cells	Vincristine	miR-23b-3p, ATG12, and HMGB2	[33]
Autophagy induction	Colon cancer cells	Cryptotanshinone Dihydrotanshinone	p53	[34]
DNA damage inhibition	Mouse embryonic fibroblasts	Etoposide	DNA–PKcs and Ku80	[35]
DNA damage inhibition	Breast and liver cancer cells	Taxol and etoposide	TMEM45A	[36]
Mitochondrial activity	Human leukemia cell line (HL-60) human lymphoma cell line (Raji)	Doxorubicin and ara-c	BAD	[37]
Mitochondrial activity	Renal carcinoma cells	Not mentioned	VHL	[38]
Mitochondrial activity	Oral squamous cell carcinoma cells	5-Fluorouracil and cisplatin	Cytochrome, Akt, and ERK	[39]
P53	Non-small-cell lung cancer cells	Cisplatin	HIF-1α and BAX	[40]

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