Review Reports

Round 1

Reviewer 1 Report

In this study, the authors have evaluated the effects of antidepressant intervention for breast cancer treatment using in vitro and in vivo models. Specifically, the impact of sertraline and citalopram, selective serotonin reuptake inhibitors (SSRIs) on breast cancer cytotoxicity, splenocyte viability, and in vivo tumour growth has been studied. Additionally, the effect of treatment using Sertraline in a chronic mild stress model associated with breast cancer has been reported.

While the research findings may add value to the field, the article requires major revisions to address several aspects associated with the study design, structure, presentation and discussion of the research data. There are 2(/3) sets of experiments – a) In vitro sertraline vs citalopram, b) in vivo CMS + sertraline (pre-treatment + continuous), c) in vivo sertraline vs citalopram that do not seem consequential in terms of parameters studied.

Introduction:

• There is lack of coherence and continuity between the paragraphs in the introduction. The authors should attempt to develop the introduction to propose the hypothesis of this study. While the cited studies may be relevant, the presentation of these studies in a disjointed manner makes it difficult to understand the purpose of this section, except for the last paragraph.
• Can the author state why two out of the several Selective serotonin reuptake inhibitors (SSRIs) have been chosen for this study?
• Similarly, did the authors consider testing the effects in more than one cell line (4T1)?
• Line 70: “The present ….. (in vivo arm)” is a very long sentence, breaking this down into simpler sentences can aid in better understanding.

 

Results and Discussion:

• Problems in understanding the choice of experimental groups in experiments I & II:
  1. Can the author justify and correlate the in vitro concentrations (uM) and in vivo doses used in this study? Is this relevant in terms of clinical doses used?
  2. Can the author conclusively say that lower Sertraline dosage is favourable in vivo studies (Exp II).
  3. Why did the authors not consider including a group with 4T1 + Sertraline (5 mg/kg/day) for Exp II? This makes it easier to compare it with Exp I. Or a naïve control group without CMS in Exp I (5 mg/kg/day) to compare against 10 mg/kg/day?
• Have the authors considered a wider range of concentrations for Citalopram in in vitro studies? Is there a reason for not including Citalopram in Exp I? The role of Citalopram seems to be insignificant across the different experiments. What value does the authors feel it adds to this manuscript?
• What are the differences between pre-treatment and continuous treatment with sertraline in in vivo experiment I?
• There are too many independent figures, the authors should consider combining figures based on experiments.

Author Response

Please see the attachment

Author Response File: Author Response.docx

Reviewer 2 Report

Researchers examined the effects of sertraline and citalopram on in vitro and in vivo models for breast cancer proliferation. The question is still interesting and affects high slice of the population. It was very interesting to see the differences between the in vivo and in vitro models- the effects are almost the opposite.

My questions:

1. Why the sertraline treatment was started 2 weeks earlier before the inoculation of tumor cells?
2. When animals died at the end of the experiment II- what caused the spontaneous death? Did they died because of their tumor mass formation?

 

Author Response

Please see attachment

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Majority of the responses provided by the authors are satisfactory. The manuscript does not require further major revisions.