Table 2.
Targeting the IL-6/JAK2/STAT3 signaling pathway in cancers.
| First author, year | Cancer type | Targeting the IL-6/JAK2/STAT3 signaling pathway | Mechanisms | Model systems |
|---|---|---|---|---|
| Kim et al., 2018 | Liver cancer | Crocin | Crocin inhibits the DNA binding activity of STAT3, thereby inhibiting the activation of STAT3 pathway and non-receptor protein tyrosine kinase, and then inhibit the gene expression regulated by STAT3 (108). | Human HCC cells (Hep3B, HepG2), human colon cancer cells (HCT116) and human BC cells (MDA-MB-231), human PCCs (BxPC3), human lung cancer cells (A549) and human OC cells (A2780). |
| Kong et al., 2021 | Bufothionine | Bufothionine induces autophagy in HCC by inhibiting JAK2/STAT3 pathway (109). | SMMC7721 and H22 cell lines. Liver and tumor tissues. H22-tumor-bearing mice model. | |
| Rodriguez-Barrueco et al., 2015 | BC | Drugs alone or in combination with HER2 inhibitors | Their inhibition of IL-6-JAK2-STAT3-calprotectin axis can reduce the tumogenesis of HR-/HER2+ BC (10). | MCF-10A and MCF-10A/ErbB2* cells. NOD.CB17-Prkdcs SCID mice model. Xenograft model. |
| Xiong et al., 2012 | CRC | TSA | The use of TSA abates JAK2/STAT3 pathway, causing CRC cells to stagnate in G1 phase, followed by apoptosis (133). | Human CRC cell lines (SW1116 and HT29). |
| Seavey et al., 2012 | JAK2 inhibitor CEP-33779 | It inhibits colorectal tumor growth by inhibiting IL-6/JAK2/STAT signal transduction (134). | Mouse model of colitis-induced CRC. | |
| Yuan et al., 2020 | Butyrate | Butyrate inhibits the development of human CRC cells by blocking the activation of IL-6/JAK2/STAT3 signaling pathway (135). | HCT-116 and HT-29 human CRC cell lines. Mouse xenograft tumor model. Tumor tissues and normal peritumoral tissues. | |
| Xu et al., 2022 | GC | BBR | BBR inhibits the proliferation of GC cells by regulating IL-6/JAK2/STAT3 related signaling pathways (141). | GC cell lines (MKN-45 and HGC-27), human gastric epithelial cells (GES-1). Tumor tissues and other tissues. Tumor xenografts. BALB/C nude mice model. |
| Sun et al., 2019 | Lung cancer | HMA | HMA inhibits the growth of A549 lung cancer cells, which is related to the induction of apoptosis and inactivation of IL-6/JAK2/STAT3 signaling pathway (20). | Human lung carcinoma H1299, human adenocarcinoma H23, mouse Lewis lung carcinoma LLC, and HUVEC cell lines; human lung carcinoma A549 and adenocarcinoma SPCA-1 cell lines. |
| Zhang et al., 2018 | PC | AG490 | AG490 attenuates TSA-mediated drug resistance of PCCs by antagonizing IL-6/JAK2/STAT3 signal transduction (4). | PC tissues. Human PCCs (PANC-1). |
| Kim et al., 2017 | OC | WP1066, TG101348 | The migration of OC cells can be inhibited by blocking the activation of JAK2 and STAT3 with neutralizing antibodies against IL-6, inhibitors WP1066 and TG101348, and silencing STAT3 with siRNA (19). | Human OC cell line SKOV3, ASCs cultured. Human subcutaneous and visceral adipose tissues from patients with benign urologic or gynecologic diseases. |
BC, breast cancer; CRC, colorectal cancer; GC, gastric cancer; PC, pancreatic cancer; OC, ovarian cancer; HCC, hepatocellular carcinoma; HER2+, HER2-positive; HR, hormone receptor; TSA, trichostatin A; BBR, Berberine; HMA, 2-hydroxy-3-methylanthraquinone; PCCs, pancreatic cancer cells; ASCs, adipose stromal cells; HUVEC, human umbilical vein endothelial.