Table 1.
Summary of STAT3 inhibitors and their mechanisms of action for OSCC treatment.
| Inhibitors | Mechanisms of Action | In Vitro Activity | In Vivo Activity | References |
|---|---|---|---|---|
| Target upstream regulators of STAT3 | ||||
| SCNE | Inhibits IL-6/STAT3 signaling pathway | Inhibits cell proliferation and migration and reduces MMP activity (SCC4, CAL27, HSC3) | Suppresses tumor growth | [119] |
| MM1 | Inhibits IL-6/STAT3 signaling pathway | Suppresses invasion and migration (SAS, OECM1) | Suppresses tumor growth | [121] |
| Honokiol | Inhibits IL-6/STAT3 signaling pathway | Suppresses cell migration, induces apoptosis, and sensitizes cells to chemotherapy (SAS, OECM1) | Suppresses tumor growth | [107,108] |
| Magnolol | Inhibits IL-6/STAT3 signaling pathway | Downregulates the self-renewal and metastasis potential of OSCC-CSCs (SAS, GNM) | NR | [120] |
| Diosmin | Inhibits IL-6/JAK1/STAT3 signaling pathway | NR | Suppresses tumor growth | [83] |
| Curcumin | Inhibits EGFR/STAT3 signaling pathway | Inhibits proliferation and invasion (SCC25) | NR | [128] |
| Alkannin | Inhibit JAK1/STAT3 signaling pathway | Restrains cell growth, migration and invasion, and facilitates apoptosis (KB) | Suppresses tumor growth | [127] |
| Roxyl-ZR | Inhibits JAK1/STAT3 signaling pathway | Inhibits metabolism, clonogenicity, proliferation, migration and invasion (UM1, TSCCA) | Suppresses tumor growth | [126] |
| All-trans retinoic acid | Inhibits JAK2/STAT3 signaling pathway | Inhibits proliferation and induces Apoptosis (CAL27, DOK) | NR | [125] |
| Licochalcone H | Inhibits JAK2/STAT3 signaling pathway | Inhibits cell growth and induces apoptosis (HN22, HSC4) | NR | [124] |
| Licochalcone D | Inhibits JAK2/STAT3 signaling pathway | Inhibits the cell growth and colony formation (HN22, HSC4) | Suppresses tumor growth | [123] |
| Compound 59 | Inhibits JAK2/STAT3 signaling pathway | Induces autophagy and apoptosis (SCC2095, SCC4) | NR | [96] |
| β-Elemene | Inhibits JAK2/STAT3 signaling pathway | Inhibits proliferation and induces apoptosis (Tca8113) | Suppresses tumor growth | [129] |
| Icaritin | Inhibits JAK2/STAT3 signaling pathway | Induces autophagy and apoptosis (CAL27, SCC9) | Suppresses tumor growth | [97] |
| Trichodermin | Inhibits STAT3 signaling pathway | Inhibits proliferation, migration and invasion (Ca922, HSC3) | Suppresses tumor growth | [130] |
| MPT0B098 | Stabilize SOCS3 | Inhibits growth and induces apoptosis (OECM1) | NR | [84] |
| GC7 | Inhibits eIF5A2/STAT3 signaling pathway | Sensitizes OSCC cells to cisplatin (CAL27, HN4, HN30, Tca8113) | NR | [131] |
| Bovine Lactoferrin | Stabilize SOCS3 | Inducts apoptosis, and suppresses Proliferation (HSC3) | NR | [132] |
| Licochalcone C | Inhibits JAK2/STAT3 signaling pathway | Induces apoptosis (HN22, HSC4) | NR | [122] |
| Betulinic acid | Inhibits STAT3 signaling pathway | Inhibits cell proliferation (KB, SAS) | Suppresses tumor growth | [133,134] |
| Koetjapic acid | Inhibits STAT3 signaling pathway | Inhibits proliferation, invasion, angiogenesis, and metastasis (SAS) | NR | [134] |
| Isoorientin | Blocking Wnt/β-catenin/STAT3 axis | Attenuates OSCC cell stemness and EMT potential (SAS, SCC25) | Suppresses tumor growth | [135] |
| Metformin | Inhibits mTOR/HIF-1α/PKM2/STAT3 pathway | Inhibits proliferation, migration and invasion (CAL27) | Suppresses tumor growth | [136] |
| Inhibits STAT3/TWIST pathway | Inhibits invasion and migration (HSC3, HSC6) | NR | [137] | |
| Strategy 2: Directly bind to STAT3 and inhibit its activation | ||||
| 4-HPR | Binds to STAT3 and inhibits its phosphorylation | Inhibits proliferation (JSCC1, JSCC2, JSCC3) | Suppresses tumor growth | [138] |
| Stattic | Binds to SH2 domain of STAT3 and inhibits phosphorylation | Inhibits invasion and migration (SCC15, SCC25) | Suppresses tumor metastasis | [109,139] |
| Strategy 3: Inhibit STAT3 phosphorylation | ||||
| Aspirin | Inhibits STAT3 phosphorylation | Induces the cell cycle arrest and apoptosis, and suppresses cell migration and invasion (Tca8113, CAL27) | NR | [140] |
| Nitidine chloride | Inhibits STAT3 phosphorylation | Induces apoptosis, and suppresses proliferation | Suppresses tumor growth | [141,142] |
| Niclosamide | Inhibits STAT3 phosphorylation | Suppresses proliferation, migration and invasion (HSC3, HSC4, WSU-HN6, Tca83) | NR | [110] |
| Bupivacaine | Inhibits STAT3 phosphorylation | Promotes apoptosis (CAL27) | Suppresses tumor growth | [143] |
| WP1066 | Inhibits STAT3 phosphorylation | Suppresses proliferation, migration and invasion (TSCCA, Tca8113) | Suppresses tumor growth | [144] |
| Anoctamin1 | Inhibits STAT3 phosphorylation | Reduces cell proliferation and migration (CAL27) | NR | [145] |
NR, not reported.