|
| Combination of natural products with gemcitabine | Experimental model | Anticancer/anticarcinogenic effects | Mechanism of action
(↓downregulated)
(↑upregulated) | Reference |
|
| Combination of 3,3-diindolylmethane with gemcitabine | PANC-1 Panc-28, and Colo-357 pancreatic cancer cells (in vitro);
PANC-1 pancreatic cancer cells orthotopic xenografts (in vivo) | Reduced the proliferation of pancreatic cancer cells | NF-κB↓, phospho-p65↓, Bcl-xL↓, XIAP↓, XIAP↓, survivin↓,
PARP cleavage↑ | [13] |
|
| Combination of thymoquinone with gemcitabine | BxPC-3 and HPAC pancreatic cancer cells (in vitro);
HPAC pancreatic cancer cells orthotopic xenografts (in vivo) | Reduced the proliferation of pancreatic cancer cells | NF-κB↓, Bcl-2 family↓,
XIAP↓, survivin↓, COX-2↓ | [14] |
|
| Combination of cucurbitacin B with gemcitabine | MiaPaCa-2, PL45, PANC-1, SU86.86, AsPC-1, Panc-03.27, and Panc-10.05 pancreatic cancer cells (in vitro);
PANC-1 pancreatic cancer cells xenografts (in vivo) | Synergistically potentiated the antiproliferative effects of pancreatic cancer cells | JAK2↓, STAT3↓, STAT5↓, cyclin A↓, cyclin B1↓, Bcl-XL↓, p21(WAF1)↑, p53↑, caspase-3↑, caspase-9↑ | [15] |
|
| Combination of sulforaphane with gemcitabine | MIA-PaCa2 pancreatic cancer cells (in vitro);
MIA-PaCa2 pancreatic cancer cells xenografts (in vivo) | Enhanced additive cytotoxic effect to pancreatic cancer cells | ALDH1↓ | [16]
|
|
| Combination of dimethylaminoparthenolide with gemcitabine | BxPC-3, PANC-1, and MiaPaCa-2 pancreatic cancer cells (in vitro);
MiaPaCa-2 pancreatic cancer cells heterotopic xenograft (in vivo) | Synergistically inhibited the proliferation of pancreatic cancer cells | NF-κB↓, IκBα↑ | [17] |
|
| Combination of dimethylaminoparthenolide with gemcitabine | MiaPaCa pancreatic cancer cells (in vitro);
MiaPaCa pancreatic cancer cells xenografts (in vivo) | Synergistically inhibited the proliferation of pancreatic cancer cells | IL-12p40↓, MCP-1↓, MIP-1β↓, eotaxin↓, TNF-α↓ | [18] |
|
| Combination of 12-O-tetradecanoylphorbol-13-acetate with gemcitabine | PANC-1 pancreatic cancer cells (in vitro);
PANC-1 tumors grown in immunodeficient mice (in vivo) | Synergistically inhibited the growth and induced apoptosis in PANC-1 cells | JNK↑ | [19] |
|
| Combination of guggulsterone with gemcitabine | MiaPaCa-2 and Panc-1 pancreatic cancer cells (in vitro);
MiaPaCa-2 pancreatic cancer cells xenografts (in vivo) | Synergistically enhanced antitumor efficacy of pancreatic cancer cells through apoptosis induction | NF-κB↓, Akt↓, BcL-2↓,
c-Jun↑, Bax↑ | [20] |
|
| Combination of monogalactosyl diacylglycerol with gemcitabine | BxPC-3, MiaPaCa2 and PANC-1 pancreatic cancer cells (in vitro) | Synergistically enhanced the growth suppression of pancreatic cancer cells | Mammalian pol α↓, γ↓, δ↓ and ε↓ | [21]
|
|
| Combination of glaucarubinone with gemcitabine | PANC-1, MiaPaCa-2, and PAN02 pancreatic cancer cells (in vitro);
PANC-1 and MiaPaCa-2 pancreatic cancer cells xenograft (in vivo) | Inhibited the growth of pancreatic cancer cells | PAK1↓, PAK4↓ | [22] |
|
| Combination of thymoquinone with gemcitabine | PANC-1, BxPC-3, and AsPC-1 pancreatic cancer cells (in vitro);
PANC-1 pancreatic cancer cells orthotopic xenograft (in vivo) | Synergistically caused an increase in pancreatic cancer cells apoptosis and tumor growth inhibition both in vitro and in vivo | Notch1↓, NICD↓, PTEN↑, p-p65↓, Bcl-2↓, Bcl-xL↓, XIAP↓, caspase-3↑, caspase-9↑, Bax↑, cytochrome c↑ | [23] |
|
| Combination of Zidovudine with gemcitabine | PK1 and KLM1 pancreatic cancer cells (in vitro);
PK1 and KLM1 pancreatic cancer cells xenografts (in vivo) | Resensitized gemcitabine-resistant pancreatic cancer cells to gemcitabine | hENT1↓, EMT-like phenotype↑, the Akt-GSK3β-Snail1 pathway↑ | [24] |
|
| Combination of piperlongumine with gemcitabine | PANC-1, BxPC-3, and AsPC-1 pancreatic cancer cells (in vitro);
BxPC-3 pancreatic cancer cells xenografts (in vivo) | Synergistically inhibited the proliferation of pancreatic cancer cells | NF-κB↓, c-Myc↓, cyclin D1↓, Bcl-2↓, Bcl-xL↓, survivin↓, XIAP↓, VEGF↓, MMP-9↓, PCNA↓, Ki-67↓, CD31↓ | [25] |
|
| Combination of escin with gemcitabine | BxPC-3 and PANC-1 pancreatic cancer cells (in vitro);
BxPC-3 pancreatic cancer cells xenografts subcutaneously established in BALB/c nude mice (in vivo) | Dramatically enhanced the suppressive effect of
pancreatic cancer cells | NF-κB↓, c-Myc↓, COX-2↓, Cyclin D1↓, Survivin↓, Bcl-2↓, Bcl-xL↓, caspase-3↑ | [26] |
|
| Combination of escin with gemcitabine | PANC-1 pancreatic cancer cells (in vitro) | Enhanced additive cytotoxic effect to pancreatic cancer cells | NF-κB↓, cyclin D↓ | [27] |
|
| Combination of gum mastic with gemcitabine | BxPC-3 and COLO 357 pancreatic cancer cells (in vitro) | Enhanced antiproliferative and apoptotic effects of pancreatic cancer cells | NF-κB↓, IκBα↑, Bax↑, Bcl-2↓ | [28] |
|
| Combination of Zyflamend with gemcitabine | AsPC-1, BxPC-3, MiaPaCa-2, and PANC-1 pancreatic cancer cells (in vitro);
MiaPaCa-2 pancreatic cancer cells orthotopic xenografts (in vivo) | Inhibited the growth of human pancreatic tumors and sensitized pancreatic cancer to gemcitabine | NF-κB↓, cyclin D1↓, c-myc↓, COX-2↓, Bcl-2↓, IAP↓, survivin↓, VEGF↓, ICAM-1↓, CXCR4↓, Ki-67↓, COX-2↓, MMP-9↓ | [29] |
|
| Combination of Japanese apricot extract (MK615) with gemcitabine | MiaPaCa-2 pancreatic cancer cells (in vitro);
MiaPaCa-2 pancreatic cancer cells xenografts (in vivo) | Significantly inhibited the growth of human pancreatic cancer cells | ROS↓ | [30] |
|
| Combination of the extract of Pao Pereira with gemcitabine | PANC-1, AsPC-1, HPAF-II, BxPC-3, and MiaPaCa-2 pancreatic cancer cells (in vitro);
PACN-1 pancreatic cancer cells xenografts (in vivo) | Enhanced the inhibitory effect of pancreatic cancer cells | Caspase-8↑, caspase-3↑, PARP↑ | [31] |
|
| Combination of Qingyihuaji formula with gemcitabine | SW1990 pancreatic cancer cells (in vitro);
SW1990 pancreatic cancer cells xenografts (in vivo) | Enhanced the antitumor activity of gemcitabine to
pancreatic cancer cells | Notch-4↓, Jagged-1↓, CD133↓ | [32] |
|
| Combination of PBI-05204 (a supercritical CO2 extract of Nerium oleander containing oleandrin) with gemcitabine | PANC-1 pancreatic cancer cells (in vitro);
PANC-1 pancreatic cancer orthotopic model (in vivo) | Markedly enhanced the antitumor efficacy of gemcitabine to pancreatic cancer cells | Ki-67↓, pAkt↓, pS6↓, p4EPB1↓ | [33] |
|
| Combination of Devil’s club Oplopanax horridus with gemcitabine | PANC-1 pancreatic cancer cells (in vitro)
| Significantly enhanced the antiproliferation activity of
gemcitabine to pancreatic cancer cells | Bcl-2↓, BAX↑, caspase-3↑ | [34] |
|
| Combination of Devil’s club Oplopanax horridus with gemcitabine | PANC-1 and BxPC-3 pancreatic cancer cells (in vitro) | Significantly enhanced the antiproliferation activity of
gemcitabine to pancreatic cancer cells | Cytochrome C↑, claspin↑, cIAP-2↑ | [35] |
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