Background
Discovery and development of novel drugs that are capable of overcoming drug resistance in tumor cells are urgently needed clinically. In this study, we sought to explore whether ivermectin (IVM), a macrolide antiparasitic agent, could overcome the resistance of cancer cells to the therapeutic drugs.
Methods
We used two solid tumor cell lines (HCT-8 colorectal cancer cells and MCF-7 breast cancer cells) and one hematologic tumor cell line (K562 chronic myeloid leukemia cells), which are resistant to the chemotherapeutic drugs vincristine and adriamycin respectively, and two xenograft mice models, including the solid tumor model in nude mice with the resistant HCT-8 cells and the leukemia model in NOD/SCID mice with the resistant K562 cells to investigate the reversal effect of IVM on the resistance in vitro and in vivo. MTT assay was used to investigate the effect of IVM on cancer cells growth in vitro. Flow cytometry, immunohistochemistry, and immunofluorescence were performed to investigate the reversal effect of IVM in vivo. Western blotting, qPCR, luciferase reporter assay and ChIP assay were used to detect the molecular mechanism of the reversal effect. Octet RED96 system and Co-IP were used to determine the interactions between IVM and EGFR.
Results
Our results indicated that ivermectin at its very low dose, which did not induce obvious cytotoxicity, drastically reversed the resistance of the tumor cells to the chemotherapeutic drugs both in vitro and in vivo. Mechanistically, ivermectin reversed the resistance mainly by reducing the expression of P-glycoprotein (P-gp) via inhibiting the epidermal growth factor receptor (EGFR), not by directly inhibiting P-gp activity. Ivermectin bound with the extracellular domain of EGFR, which inhibited the activation of EGFR and its downstream signaling cascade ERK/Akt/NF-κB. The inhibition of the transcriptional factor NF-κB led to the reduced P-gp transcription.
6.4.4. Medical or scientific experimentation or treatment
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Category: Covid Human Rights
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Created: Tuesday, 10 May 2016 13:21
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Written by Judicial College of Victoria
6.4.4. Medical or scientific experimentation or treatment - Scope of the right
- Section 10(c) prohibits ‘medical or scientific experimentation or treatment’ of a person without their ‘full, free and informed consent’.
- Article 7 of the ICCPR requires that a person must not be subjected to medical or scientific experimentation ‘without his free consent’. The European Convention on Human Rights contains no equivalent of s 10(c).
- Section 10(c) goes further than the ICCPR and prohibits treatment without consent as well as experimentation. Although the prohibition against medical treatment without consent is not explicit in the ICCPR, or in the European Convention on Human Rights, it has been considered under the rights relating to inhuman or degrading treatment, liberty and security (Kracke v Mental Health Review Board (2009) 29 VAR 1; [2009] VCAT 646 [548]). The ACT and New Zealand human rights legislation, like the Charter, explicitly prohibit medical treatment without consent.
- The meaning of the word ‘treatment’ is broad, see 6.4.3. Cruel, inhuman or degrading treatment or punishment.
- Imposing a condition of bail requiring the accused to obtain medical treatment potentially engages this right (Woods v DPP (2014) 238 A Crim R 84; [2014] VSC 1 [15], [68]–[70]).