Table 1.

Summary of 17 preclinical studies identified.

References	In vitro/in vivo	Cell culture/Disease model	Endpoint studied	Animal allocation and Flow described	Randomized	Blinded	Main findings
Banerjee et al., 2013	Both	MIA-PaCa2 was obtained from the ATCC. Female nude mice (4–6 weeks old) were used (Charles River Laboratories).	To study the effect of OGT inhibition on PC cells.	Yes	Yes	Unclear	The authors observed that down-regulation of Sp1 by mithramycin, siRNA, TL resulted in decreased NF–κB activity in both cell lines and animal models.
Chen et al., 2013	Both	MIA PaCa-2 cells derived from a primary pancreatic tumor were obtained from Ascites-derived AsPC-1. Three de-identified human tumors were implanted subcutaneously into SCID animals (Jackson Laboratory).	Mcl-1 and miR-204 expression in PC cells in vitro and in vivo.	Yes	Unclear	Unclear	TL mediated miR-204 increase causes PC cell death via loss of Mcl-1.
Wang, 2012	In vitro	ASPC-1 was purchased from the ATCC.	To detect the expression changes of PARP and caspase-3.	NA	NA	NA	The proliferation of AsPC-1 cells was inhibited by TL.
Borja-Cacho et al., 2010	In vitro	MIA-PaCa2 and PANC-1 cells were obtained from the ATCC.	To explore cell viability, apoptosis, caspase-3 and caspase-9 activities, and poly(ADP)-ribose polymerase cleavage.	NA	NA	NA	TL and TNF-related apoptosis-inducing ligand decreased the cell viability in all the cell lines and increased apoptotic cell death as a result of caspase-3 and caspase-9 activation.
Ding et al., 2015	Both	The PANC1, ASPC1 and SW1990 were purchased from the ATCC (Rockville, MD, USA). Athymic nude mice (5-weekoldfemales) were purchased from Shanghai Laboratory Animal Center of Chinese Academy of Science (Shanghai, China).	To measure expression of HIF-1α and VEGF.	Yes	Unclear	Unclear	The expression of HIF-1α was shown to be reduced in pancreatic cell lines following treatment with TL.
Dudeja et al., 2009	In vitro	Panc-1 and MiaPaCa-2 were a kind gift from Dr Edward E. Whang (Brigham and Women's Hospital, Harvard Medical School, Boston, MA).	To measure intracellular Ca2, cytosolic cathepsin B activity, caspase-3 activity, cell viability, and lysosome integrity.	NA	NA	NA	HSP70 expression was down-regulated in cultured PC cells by exposure to TL.
Liu and Cui, 2013	Both	PANC-1, CFPAC-1 and normal pancreatic cell line HPC-Y5, were obtained from the ATCC (Manassas, VA, USA). Five-week-old male BALB/c athymic nude mice were obtained from Shanghai Laboratory Animal Center of Chinese Academy of Sciences.	In vitro, cell viability and apoptosis were analyzed. In vivo, inhibitory effects of TL were assessed.	Yes	Yes	Unclear	The combination Of tl and artesunate can exert synergistic anti-tumor effects in PC cells.
Ma et al., 2013	Both	PANC-1 was obtained from the ATCC (Manassas, VA, USA) Four- to 6-week-old BALB/c nude mice were obtained from Shanghai SLAC Laboratory Animal Co., Ltd. (Shanghai, China).	To measure cell viability and apoptosis, and to examine the expression of COX-2 and VEGF.	Yes	Yes	Unclear	TL induces apoptosis and inhibits proliferation of PANC-1 PC cells by downregulating COX-2 and VEGF.
Mackenzie et al., 2013	Both	MIA PaCa-2, Capan-1, and HEK-293 lines were obtained from the ATCC. Female SCID mice were used (The Jackson Laboratory, Bar Harbor, ME).	To measure miR-142-3p and HSPA1B (HSP70) levels.	Yes	Yes	Unclear	TL downregulated HSP70, and induced the expression of miR-142-3p.
Mujumdar et al., 2010	In vitro	MIA-PaCa2 and PANC-1 cells were obtained from the ATCC.	To measure viability of PC cells, and to examine Caspase-3, Atg5, and Beclin1 levels.	NA	NA	NA	TL kills PC cells by 2 different pathways. It induces caspase-dependent apoptotic death in Mia- PaCa-2, Capan-1, and BxPC-3, and induces caspase independent autophagic death in S2-013, S2-VP10, and Hs766T.
Mujumdar et al., 2014	In vitro	MIA PaCa-2 was obtained from the ATCC.	To investigate the GRP78 expression in PC cells.	NA	NA	NA	TL kills PC cell lines by inducing the UPR, resulting in ER stress by inhibiting expression of the survival protein GRP78.
Phillips et al., 2007	Both	MIA-PaCa2 and PANC-1 cells were obtained from the ATCC. Female nude mice (4–6 weeks old) were used (Charles River Laboratories).	To examine the effects of TL on (a) PC cells by assessing viability and apoptosis, (b) PC growth and local invasion in vivo, and (c) HSP70 levels in PC cells.	Yes	Yes	Yes	TL causes PC cell death by the induction of apoptosis, and its mechanism of action is mediated via the inhibition of HSP70.
Qiao et al., 2016	In vitro	BxPC.-3 and PANC.-1 cell lines were obtained from the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences. (Shanghai, China).	To investigate the CHK1 expression in PC cells.	NA	NA	NA	TL synergistically increased gemcitabine–induced cell growth inhibition and apoptosis, in addition to the cooperative regulation of B–cell lymphoma2 family proteins and loss of mitochondrial membrane potential.
Wang et al., 2006	In vitro	HeLa (CCL-2), PANC-1 (CRL-1469), and RAW264.7 (TIB-71) cells were purchased from ATCC (Manassas, VA, USA).	To examine the effect of TL on the growth of pancreatic carcinoma PANC-1 and cervical adenocarcinoma HeLa cells.	NA	NA	NA	The authors found that TL potently induces apoptosis through activating the caspase cascade associated with Bid cleavage.
Wang et al., 2012	Both	AsPC-1, MiaPaCa-2, BxPC-3, PANC-1 and SW480 were obtained from ATCC (Manassas, VA, USA). Athymic mice without detailed descriptions.	To examine the effect of TPL on cell growth inhibition and apoptosis of PC cells in vitro and in vivo, and further explore the regulatory role of DcR3 in TPL-induced apoptosis pathway.	Yes	Yes	Unclear	TPL inhibited the proliferation and induced the apoptosis of PC cells, also inhibited DcR3 expression.
Zhou et al., 2007	In vitro	ASPC-1, PANC-1 and SW1990 were purchased from the ATCC (Rockville, MD).	To investigate the effects of TL on proliferation and apoptosis of PC cells.	NA	NA	NA	TL significantly down-regulated 5-lipoxygenase (5-LOX) expression, as well as downstream leukotriene B4 (LTB4) production, in PC cell lines.
Zhou et al., 2008	In vitro	SW1990 was obtained from Professor Wang Xing Peng (Shanghai, China).	To investigate the inhibitory effects of TL on apoptosis and angiogenesis of PC.	NA	NA	NA	TL induced the apoptosis in human PC cells by up-regulating the expression of apoptosis associated caspase-3 and bax gene.

ATCC, American Type Culture Collection; COX-2, cyclooxygenase-2; NA, not applicable; PC, pancreatic cancer; SCID, severe combined immunodeficient; TL, TL; VEGF, vascular endothelial growth factor.