GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Acylated Ghrelin Renders Chemosensitive Ovarian Cancer Cells Resistant to Cisplatin Chemotherapy via Activation of the PI3K/Akt/mTOR Survival Pathway.
El-Kott. Attalla Farag AF; Shati. Ali A AA; Al-Kahtani. Mohammed Ali MA; Alqahtani. Sultan S
Key Findings
- Acylated ghrelin (AG) boosts survival and proliferation of chemosensitive ovarian cancer cells and makes them resistant to cisplatin.
- The protective effect is driven by activation of the PI3K/Akt/mTOR and NF‑κB pathways and a reduction in pro‑apoptotic proteins like p53 and caspase‑3.
- Blocking the ghrelin receptor with [D‑Lys3]-GHRP‑6 or inhibiting PI3K with LY294002 completely reverses the survival advantage conferred by AG.
Practical Outcomes
- For biohackers and self‑experimenters, this signals a potential safety risk: using ghrelin‑mimicking peptides (e.g., GHRP‑6) could unintentionally support cancer cell survival, especially in people with undiagnosed or high‑risk tumors. It suggests caution or avoidance of chronic ghrelin agonist use unless more safety data are available.
Summary
The study found that giving synthetic ghrelin (the hormone that makes you feel hungry) to ovarian cancer cells actually helps those cells survive and become resistant to the chemotherapy drug cisplatin. This protective effect works through well‑known cell‑growth pathways (PI3K/Akt/mTOR and NF‑κB) and can be blocked by a ghrelin‑receptor blocker or a PI3K inhibitor.
Abstract
This study investigated the effect of acylated synthetic ghrelin (AG) on the survival and proliferation of human chemosensitive ovarian cancer cells (A2780) and explored some mechanisms of action with a focus on the p53 apoptotic pathway and PI3K/Akt and NF-<i>κ</i>B survival pathways. Human A2780 ovarian cancer cells were cultured with or without AG treatment in the presence or absence of cisplatin. In some cases, cisplatin+AG-treated cells were pre-incubated either with [D-Lys3]-GHRP-6, a ghrelin receptor antagonist, or with LY294002, a PI3K inhibitor. mRNA of ghrelin receptors(GHS-R1a and GHS-R1b), as well as, protein levels of GHS-R1a, were expressed abundantly in A2780 cells. AG treatment did not affect the mRNA and protein levels of GHS-R1a and GHS-R1b in both control and Cis-treated cells. However, while AG treatment had no effect on control cell viability, it significantly increased cell viability and proliferation and inhibited cell death in Cis-treated cells. In both control and Cis-treated cells, AG treatment significantly increased PI3K/Akt/mTOR signaling and enhanced the nuclear accumulation of NF-<i>κ</i>B. Concomitantly, in both control and Cis-treated cells, AG significantly lowered the protein levels of p53, p-p53 (Ser16), PUMA, cytochrome C, and cleaved caspase-3. Interestingly, pre-incubating the cells with either [D-Lys3]-GHRP-6 or LY294002 completely abolished the above-mentioned effect of AG in both control and Cis-treated cells. In conclusion, the findings of this study show that AG promotes cell survival of the OC cells and renders them resistat to Cis therapy, an effect that is mediated by the activation of PI3K/Akt/mTOR and activation of NF-<i>κ</i>B, and requires GHS-R1a.
Study Information
pubmed
2019
2019-07-08T00:00:00.000Z
10.1155/2019/9627810
15
49