Table 3.

The most important anticancer synergistic effects of cucurbitacin B in combination with chemotherapeutic drugs

Type of cancer	Type of chemotherapeutic agents combined with cucurbitacin B	Experimental model	Main results	Refs.
Breast cancer	Imatinib mesylate	In vitro MCF-7 cells	Anticancer synergistic effects ↓cell proliferation ↑apoptosis	[86]
	Gemcitabine docetaxel	In vitro MDA-MB-231 cells	Synergistic effects ↓cell proliferation, ↑apoptosis	[87]
		In vivo mice	↓tumour volume No signs of increased toxicity
	Ionizing radiation	In vitro 4T1 cells	Blocks cancer cells in the G2/M phase ↑apoptosis, ↓cancer cells growth ↓p-STAT3, ↓c-Myc, ↓Bcl-2, ↓Bcl-xL, ↑caspase-9, ↑p21, ↑p53	[88]
Pancreatic cancer	SCH772984, an ERK inhibitor	In vitro HPAC cells	↑apoptosis, ↓cancer cells growth ↓EGFR, ↓PI3K/Akt/mTOR, ↓STAT3, ↑Bim, ↓McL-1, ↓Bcl-2, ↓Bcl-xl, ↓survivin, ↑cucurbitacin B sensitivity	[89]
		In vivo mice	↓ tumour growth
Colorectal cancer	Gefitinib	In vitro HT-29, HCT-116 cells	Cell cycle inhibition ↑apoptosis, ↓EGFR, ↓JAK/STAT	[90]
	Imatinib mesylate	In vitro SW480 cells	↓cell proliferation ↑apoptosis ↓MMP-2, ↑degradation of extracellular matrix	[86]
Ovarian cancer	Cisplatin	In vitro A2780 cells	Cytotoxicity against the ovarian cancer cell line	[91]
	Paclitaxel	In vitro A2780/Taxol cells	Dose- and time-dependent cytotoxicity effect ↑G2/M phase arrest of the cell cycle, ↑p53, ↑p21, ↓Bcl-2, ↓caspase-3, ↓P-gp	[92]
Osteosarcoma	Methotrexate	In vitro human osteosarcoma cells	↓AKT, ↓mTOR	[93]

↑ increase, ↓decrease, JAK: Janus kinase; McL-1: induced myeloid leukaemia cell differentiation protein 1; Bim: Bcl-2-like protein 11