Multidrug resistance mediated by overexpression of P-glycoprotein in human osteosarcoma in vivo.

Suto, Ryuji; Abe, Yoshiyuki; Nakamura, Masato; Ohnishi, Yasuyuki; Yoshimura, M; Lee, Y H; Imanishi, Takashi; Yamazaki, Hitoshi; Kijima, Hiroshi; Tokunaga, Tetsuji; Oshika, Y; Hiraoka, Nobuyoshi; Tamaoki, Norikazu; Fukuda, Hiroki; Ueyama, Yoshito

doi:10.3892/ijo.12.2.287

Cited by 7 publications

(6 citation statements)

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“…To further address the difference in potency between E9 and THZ531, we analyzed the expression of the multidrug resistance family of drug-transporter proteins in our panel of OS cell lines. ABCB1, which was previously shown to mediate THZ531 resistance in neuro blastoma cells (17), was overexpressed in all the OS cell lines tested, in keeping with prior reports of its upregulation in OS cell lines and drug-resistant tissues (Supplemental Figure 4B) (30)(31)(32)(33)(34). Addition of the ABCB1 inhibitor tariquidar (35) significantly increased sensitivity to THZ531 in 6 out of 9 cell lines, whereas the sensitivity to E9 did not change substantially upon addition of tariquidar (Supplemental Figure 4, A and C).…”

Section: Resultssupporting

confidence: 86%

Ex vivo screen identifies CDK12 as a metastatic vulnerability in osteosarcoma

Bayles¹,

Krajewska²,

Pontius³

et al. 2019

Journal of Clinical Investigation

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Section: Resultssupporting

confidence: 86%

Ex vivo screen identifies CDK12 as a metastatic vulnerability in osteosarcoma

Bayles¹,

Krajewska²,

Pontius³

et al. 2019

Journal of Clinical Investigation

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“…The overexpression of MDR1 (P-gp) is an important mechanism of this resistance. The role of the MDR1 (P-gp) gene in the MDR of osteosarcoma has been confirmed (10,11). We verified that the Saos-2/R cell subline has cross-resistance characteristics.…”

Section: Discussionmentioning

confidence: 53%

Diallyl trisulfide reverses drug resistance and lowers the ratio of CD133+ cells in conjunction with methotrexate in a human osteosarcoma drug-resistant cell subline

Liu²,

Zhao³

et al. 2009

Mol Med Rep

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Abstract. P-glycoprotein (P-gp) overexpression and tumor stem cells are thought to be important factors in the crossresistance of cancer cells. There have been no studies on whether diallyl trisulfide (DATS) can reverse drug resistance in human osteosarcoma cells. In the present study, we demonstrated that DATS down-regulated P-gp expression and reversed drug resistance. DATS and methotrexate (MTX) decreased the ratio of drug-resistant human osteosarcoma cells positive for CD133 (a tumor stem cell marker). To the best of our knowledge, this is the first evidence that DATS can reverse drug resistance and lower the ratio of CD133 + cells in human osteosarcoma cells in conjunction with MTX.

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“…It has been reported that MDR can be mediated by Pgp in osteosarcoma (45). We observed that the long-term treatment of osteosarcoma cells with paclitaxel induced Pgp overexpression.…”

Section: Discussionmentioning

confidence: 51%

Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing Pgp overexpression through the inhibition of NF-κB signaling

Sun

2017

International Journal of Molecular Medicine

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The development of multidrug resistance (MDR) remains a major limitation to successful chemotherapy in osteosarcoma. Preventing the introduction of MDR has been a research hotspot in clinical and investigational oncology. The aim of this study was to evaluate the preventive effects of tetrandrine (TET) against MDR in osteosarcoma. For this purpose, U-2OS human osteosarcoma cells were treated with paclitaxel alone or a combination of paclitaxel with TET. The cells treated with paclitaxel alone eventually acquired MDR along with the overexpression of and highly activated P-glycoprotein (Pgp), while the cells treated with the paclitaxel-TET combination were sensitive to chemotherapeutic drugs and expressed decreased levels of Pgp and less Pgp activity. The promoter activities of MDR gene 1 (MDR1) and nuclear factor (NF)‑κB, and the expression levels of NF-κB and p-IκB-α were all enhanced in the cells cultured with paclitaxel alone. NF-κB DNA-binding activity and the binding ability of NF-κB to the MDR1 promoter were also enhanced in the cells cultured with paclitaxel alone compared to the control cells. However, the expression and activity of NF-κB were significantly decreased in the paclitaxel-TET combination-treated group as compared with the cells treated with paclitaxel alone. On the whole, our findings suggest that TET prevents paclitaxel-induced MDR by inhibiting Pgp overexpression through a mechanism that may involve the inhibition of NF-κB signaling in osteosarcoma.

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Multidrug resistance mediated by overexpression of P-glycoprotein in human osteosarcoma in vivo.

Cited by 7 publications

References 0 publications

Ex vivo screen identifies CDK12 as a metastatic vulnerability in osteosarcoma

Ex vivo screen identifies CDK12 as a metastatic vulnerability in osteosarcoma

Diallyl trisulfide reverses drug resistance and lowers the ratio of CD133+ cells in conjunction with methotrexate in a human osteosarcoma drug-resistant cell subline

Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing Pgp overexpression through the inhibition of NF-κB signaling

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