Table 2.
A schematic diagram of the expression of hypoxic and drug resistance factors.
| Study. (year). Ref | Source | Mechanism | Target gene | Expression change | Clinic characters relatedness |
|---|---|---|---|---|---|
| Wang et al.(2019) (22) | MG-63 and U2-os cells | Visfatin was involved in cisplatin resistance of OS cells by upregulating expression of Snail via HIF-1α induced transcription | Snail and its mRNA | ↑ | cisplatin resistance |
| Keremu et al.(2019) (23) | 20 osteosarcoma patient samples and human OS cell lines (MG-63, U-2OS and SaoS-2) | Overexpression of miR-199a resensitizes cisplatin resistant cells to cisplatin through inhibition of HIF-1α | miR-199a | ↑ | cisplatin resistance |
| Zheng et al.(2017) (24) | U-2OS (derived from bone tissues of a 15-year-old OS patient) and MG-63 (derived from bone tissues of a 14-year-old OS patient) cells | HIF-1α-induced Mxd1 up-regulation suppresses the expression of PTEN under hypoxia, which leads to the activation of PI3K/AKT antiapoptotic and survival pathway | Mxd1 | ↑ | hypoxia-induced cisplatin resistance |
| Guo et al.(2017) (25) | MG63, U2OS and 143B cells | MiR-335 targets CSCs and regulates OS stem cell-like properties via downregulated POU5F1 to synergize with chemotherapeutic drugs | miR-335 | ↓ | stem cell-like properties |
| Ma et al.(2017) (26) | Human OS cells (SOSP-9607, MG-63, SaOS-2) | Hypoxia increased the expression of MRG and enhanced the sensitivity of EPI and IFO in OS patients | SKA1 | ↓ | chemotherapy resistance |
| Zhao et al.(2016) (27) | MG-63 and U2-os cells | Hypoxia reduced sensitivity to Dox by promoting the AMPK signaling and has no association with HIF-1α | AMPK | ↑ | Dox resistance and Dox-induced apoptosis |
| Zhou et al.(2016) (28) | human OS cell lines (MG-63, U-2OS and SaoS-2) | Hypoxia induced microRNA-488 expression to promote proliferation, reduce apoptosis and decrease the Dox sensitivity of OS cells | microRNA-488 | ↑ | tumor proliferation, apoptosis and Dox resistance |
| Wang et al.(2016) (29) | human OS cell lines MG-63, U2OS, Saos-2 and normal os- teoblastic cell line HOB |
miR-367 suppressed the increase of KLF4 induced by ADR in OS cells, as well as Bax and cleaved caspase-3 | MiR-367 | ↑ | ADR-induced apoptosis |
| Lin et al.(2016) (30) | U2OS and G293 cell lines | miR-202 promotes chemotherapy resistance by targeting PDCD4 | miR-202 | ↑ | Dox resistance and Dox-induced apoptosis |
| Xu et al.(2016) (31) | MG-63 cell line and Dox-resistant cell line (Mg-63/Dox) | miR-30a downregulated in Mg-63/Dox and miR-30a reduced chemoresistance via suppressing Beclin-1-mediated autophagy | miR-30a | ↓ | chemoresistance and autophagy |
| Li et al.(2016) (32) | human MG-63 OS cells | Notch signaling is up-regulated in human OS cells under hypoxia and Notch1 may represent a viable target to overcome chemoresistant OS cells in a hypoxic niche by regulating MRP1 gene expression. |
Notch1 and MRP1 | ↑ | chemoresistant |
| Guo et al.(2015) (33) | human MG-63 OS cells | HIF-1α inhibitor combined with paxilitaxel blocked autophagy and augmented the anti-tumor effects. | — | — | paxilitaxel-induced apoptosis |
| Zhang et al.(2015) (34) | human OS cell lines (MG-63 and U-2OS) | miR-301a and HMGCR were up-regulated in chemotherapy-resistant OS, subsequently reduced Dox-induced cell apoptosis and contributed to chemoresistance of OS cells |
miR-301a | ↑ | Dox resistance and Dox-induced apoptosis |
| Roncuzzi et al.(2014) (35) | human MG-63 OS cells | HIF-1α hindered Dox-induced apoptosis and promoted the outward transport of intracellular Dox by activating P-gp expression in OS in normoxic conditions | c-Myc | ↓ | Dox-induced apoptosis |
| p21 | ↑ | Dox-induced apoptosis | |||
| MDR-1/P-gp | ↑ | Dox resistance | |||
| Scholten et al.(2014) (36) | Human OS cells (143B, MNNG/HOS, MG-63) | Hypoxic OS cells can be sensitized to Dox treatment by inhibition of the Wnt/β-catenin signaling pathway | Wnt/β-catenin signaling pathway | ↓ | Dox-mediated toxicity |
*CSCs, cancer stem cells; ADR, adriamycin; Dox, Dox;↑, upregulated; ↓, downregulated.