Monepantel considerably enhances the therapeutic potentials of PEGylated liposomal doxorubicin and gemcitabine in ovarian cancer: in vitro and in vivo studies
Authors: Javed Akhter
Krishna Pillai
Parvin Ataie-Kachoie
David Lawson Morris
Samina Badar
Journal: American journal of cancer research (2018)
Discipline: CLINICAL MEDICINE
Keywords: Monopentel; combination therapy; doxorubicin; gemcitabine; ovarian cancer.
Affiliations: Department of Surgery, University of New South Wales, St. George Hospital Kogarah, Nsw, Australia.

Abstract:  Ovarian cancer is a lethal disease since treated patients often die from relapse. Resistance to current treatment regime involving doxorubicin and gemcitabine is well known. Hence, we set forth to develop a more effective therapy by combining current treatment drugs with monepantel, an antihelminth drug with proven anticancer effect. In vitro cytotoxicity were first investigated with pegylated liposomal doxorubicin (PLD), gemcitabine, monepantel as single agents and then in combination with monepantel on ovarian tumor cells. Drug effect on oncogenic proteins was determined by western blot analysis and resistance to drugs by colony formation assays. Using in vivo model (nude mice), a similar study, as above, was carried out to determine correlation to in vitro findings. Close correlation existed between in vitro and in vivo studies with the latter indicating that combination of monepantel with either low or high dose PLD was more effective compared to single drug therapy. A similar finding existed for gemcitabine, with gemcitabine showing a more superior efficacy (100% ablation) in combination with MPL. Western blot analysis indicated p-mTOR, p70s6K and 4E-BP1 were severely inhibited by combination of MPL with either PLD or gemcitabine. Colony formation assay indicated a dramatic reduction of colonies with combination treatment suggesting a considerable reduction of resistance. After 28 days, treatment using a combination of MPL with either PLD or gemcitabine showed tumor regression. Hence, the combination of gemcitabine or doxorubicin with monepantel may serve as a more effective therapy for ovarian cancer. 

Retracted: No

PubPeer comments:
 There is an instance of image duplication in this paper. Figure 2A contains the same image twice. The OVCAR-3 cell line data (bottom row) has the same image in the doxorubicin and gemcitabine treated samples. See the red boxes in the attached image ![file] , 
 #1 Dear Yermo, Thank you very much for making us aware of this. This scientist is no longer part of our group but I will refer to our laboratory record books to review the data for this experiment and rectify as soon as possible. Thank you. David , 
 Letu2019s play count the lanes! GAPDH is 3 lanes short in Figure 3A. Could the authors please post the original uncropped scans? You may post a link here to an external site (such as Imgur.com or Google Drive) to provide readers access to larger original images. As the first author appears to have left this lab, perhaps Dr. Morris could investigate that authoru2019s papers. I have found issues which each I have reviewed. *** ![file] , 
 Response from recent email to journal: Thank you for contacting AJCR regarding your concerns of the paper published in Am J Cancer Res. 2018; 8(10): 2064u20132075. We will contact the authors for clarification, and if the response is not satisfactory we will initiate an editorial retraction. We at AJCR take scientific integrity seriously and wonu2019t tolerate any scientific misconduct. We will let you know the final decision. Thank you for your support to AJCR. Editor s Office American Journal of Cancer Research www.ajcr.us ,