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Original Research

Astragalus IV Undermines Multi-Drug Resistance and Glycolysis of MDA-MB-231/ADR Cell Line by Depressing hsa_circ_0001982-miR-206/miR-613 Axis

, , , , , , , , & show all
Pages 5821-5833 | Published online: 22 Jul 2021

Figures & data

Figure 1 Proliferation (A), migration (B), invasion (C), and expressions of hsa_circ_0001982/miR-206/miR-613 axis (D) were determined in the BT-549/ADR cell line, MDA-MB-468/ADR cell line, and MDA-MB-231/ADR cell line after astragaloside IV treatment. (AC) *P<0.05 in comparison to control group. (D) *P<0.05.

Figure 1 Proliferation (A), migration (B), invasion (C), and expressions of hsa_circ_0001982/miR-206/miR-613 axis (D) were determined in the BT-549/ADR cell line, MDA-MB-468/ADR cell line, and MDA-MB-231/ADR cell line after astragaloside IV treatment. (A–C) *P<0.05 in comparison to control group. (D) *P<0.05.

Figure 2 Astragaloside IV relieved multi-drug resistance and glycolysis of the MDA-MB-231/ADR cell line. (A) Effect of astragaloside IV on gemcitabine-, adriamycin-, oxaliplatin-, and cisplatin-resistances of the MDA-MB-231/ADR cell line. *P<0.05 in comparison to NC group. (BE) Glucose uptake (B), lactate production (C), extracellular acidification rate (ECAR) (D), and oxygen consumption rate (OCR) (E) of the MDA-MB-231/ADR cell line were evaluated after exposure to astragaloside IV. *P<0.05 in comparison to the NC group.

Figure 2 Astragaloside IV relieved multi-drug resistance and glycolysis of the MDA-MB-231/ADR cell line. (A) Effect of astragaloside IV on gemcitabine-, adriamycin-, oxaliplatin-, and cisplatin-resistances of the MDA-MB-231/ADR cell line. *P<0.05 in comparison to NC group. (B–E) Glucose uptake (B), lactate production (C), extracellular acidification rate (ECAR) (D), and oxygen consumption rate (OCR) (E) of the MDA-MB-231/ADR cell line were evaluated after exposure to astragaloside IV. *P<0.05 in comparison to the NC group.

Figure 3 The sponging relationship between hsa_circ_0001982 and miR-206/miR-613 in the MDA-MB-231/ADR cell line. *P<0.05. (A and B) Expressions of miR-206 (A) and miR-613 (B) were, respectively, detected in MDA-MB-231/ADR cells after separate transfection of miR-206/miR-613 mimic and inhibitor. *P<0.05. (C) The target sites of hsa_circ_0001982 and miR-206 were displayed, and luciferase activity of MDA-MB-231/ADR cells was reduced in the pGL3-hsa_circ_0001982 Wt+miR-206 mimic group as compared with the pGL3-hsa_circ_0001982 Mut+miR-206 mimic group and the pGL3-hsa_circ_0001982 Wt+miR-NC group. *P<0.05. (D) MiR-613 was sponged by hsa_circ_0001982 in certain sites, and luciferase activity of MDA-MB-231/ADR cells was decreased in the pGL3-hsa_circ_0001982 Wt+miR-613 mimic group as compared with the pGL3-hsa_circ_0001982 Mut+miR-613 mimic group and pGL3-hsa_circ_0001982 Wt+miR-NC group. *P<0.05. (E) Hsa_circ_0001982 expression in MDA-MB-231/ADR cells was measured after silencing of hsa_circ_0001982. *P<0.05. (F) MiR-206/miR-613 expression in MDA-MB-231/ADR cells was altered after silencing of hsa_circ_0001982. *P<0.05.

Figure 3 The sponging relationship between hsa_circ_0001982 and miR-206/miR-613 in the MDA-MB-231/ADR cell line. *P<0.05. (A and B) Expressions of miR-206 (A) and miR-613 (B) were, respectively, detected in MDA-MB-231/ADR cells after separate transfection of miR-206/miR-613 mimic and inhibitor. *P<0.05. (C) The target sites of hsa_circ_0001982 and miR-206 were displayed, and luciferase activity of MDA-MB-231/ADR cells was reduced in the pGL3-hsa_circ_0001982 Wt+miR-206 mimic group as compared with the pGL3-hsa_circ_0001982 Mut+miR-206 mimic group and the pGL3-hsa_circ_0001982 Wt+miR-NC group. *P<0.05. (D) MiR-613 was sponged by hsa_circ_0001982 in certain sites, and luciferase activity of MDA-MB-231/ADR cells was decreased in the pGL3-hsa_circ_0001982 Wt+miR-613 mimic group as compared with the pGL3-hsa_circ_0001982 Mut+miR-613 mimic group and pGL3-hsa_circ_0001982 Wt+miR-NC group. *P<0.05. (E) Hsa_circ_0001982 expression in MDA-MB-231/ADR cells was measured after silencing of hsa_circ_0001982. *P<0.05. (F) MiR-206/miR-613 expression in MDA-MB-231/ADR cells was altered after silencing of hsa_circ_0001982. *P<0.05.

Figure 4 Hsa_circ_0001982-miR-206/miR-613 axis manipulated multi-drug resistance (A), migration (B), invasion (C), proliferation (D), and glycolysis, indicated by glucose uptake (E), lactate production (F), extracellular acidification rate (ECAR) (G), and oxygen consumption rate (OCR) (H), of MDA-MB-231/ADR cell line. (AC) *P<0.05. (D) *P<0.05 in comparison to the NC group; #P<0.05 in comparison to the si-hsa_circ_0001982 transfection group. (E and F) *P<0.05. (G and H) *P<0.05 in comparison to the NC group; #P<0.05 in comparison to the si-hsa_circ_0001982 transfection group.

Abbreviations: GEM, gemcitabine; ADM, adriamycin; OXA, oxaliplatin; DDP, cisplatin.
Figure 4 Hsa_circ_0001982-miR-206/miR-613 axis manipulated multi-drug resistance (A), migration (B), invasion (C), proliferation (D), and glycolysis, indicated by glucose uptake (E), lactate production (F), extracellular acidification rate (ECAR) (G), and oxygen consumption rate (OCR) (H), of MDA-MB-231/ADR cell line. (A–C) *P<0.05. (D) *P<0.05 in comparison to the NC group; #P<0.05 in comparison to the si-hsa_circ_0001982 transfection group. (E and F) *P<0.05. (G and H) *P<0.05 in comparison to the NC group; #P<0.05 in comparison to the si-hsa_circ_0001982 transfection group.

Figure 5 MiR-206 and miR-613 restored effects of astragaloside IV on multi-drug resistance (A), migration (B), invasion (C), proliferation (D), glucose uptake (E), lactate production (F), extracellular acidification rate (ECAR) (G), and oxygen consumption rate (OCR) (H) of the MDA-MB-231/ADR cell line. (A) *P<0.05 in comparison to the NC group; #P<0.05 in comparison to the si-hsa_circ_0001982 transfection group. (B and C) *P<0.05. (D) *P<0.05 in comparison to the NC group; #P<0.05 in comparison to the si-hsa_circ_0001982 transfection group. (E and F) *P<0.05. (G and H) *P<0.05 in comparison to the NC group; #P<0.05 in comparison to the si-hsa_circ_0001982 transfection group.

Abbreviations: GEM, gemcitabine; ADM, adriamycin; OXA, oxaliplatin; DDP, cisplatin.
Figure 5 MiR-206 and miR-613 restored effects of astragaloside IV on multi-drug resistance (A), migration (B), invasion (C), proliferation (D), glucose uptake (E), lactate production (F), extracellular acidification rate (ECAR) (G), and oxygen consumption rate (OCR) (H) of the MDA-MB-231/ADR cell line. (A) *P<0.05 in comparison to the NC group; #P<0.05 in comparison to the si-hsa_circ_0001982 transfection group. (B and C) *P<0.05. (D) *P<0.05 in comparison to the NC group; #P<0.05 in comparison to the si-hsa_circ_0001982 transfection group. (E and F) *P<0.05. (G and H) *P<0.05 in comparison to the NC group; #P<0.05 in comparison to the si-hsa_circ_0001982 transfection group.

Figure 6 Astragaloside IV down-regulated hsa_circ_0001982, thereby disordering binding between hsa_circ_0001982 and miR-206/miR-613. Consequently, multi-drug resistance, glycolysis, migration, and invasion of the drug-resistant TNBC cell line (ie, MDA-MB-231/ADR) were weakened.

Figure 6 Astragaloside IV down-regulated hsa_circ_0001982, thereby disordering binding between hsa_circ_0001982 and miR-206/miR-613. Consequently, multi-drug resistance, glycolysis, migration, and invasion of the drug-resistant TNBC cell line (ie, MDA-MB-231/ADR) were weakened.