Abstract
The application of chemotherapy in non-small cell lung cancer (NSCLC) is limited by the toxicity to normal cells and the development of multi-drug resistance.
Targeted chemotherapy using cytotoxic analogs against specific receptors on cancer cells could be a less toxic and more efficacious approach. We identified that the expressions of somatostatin receptor (SSTR) 2 and 5 in tumor tissues from NSCLC patients were higher than those in the adjacent normal tissues by immunohistochemistry, and therefore, cytotoxic somatostatin analogues might be applied for SSTRs-mediated targeted therapy against NSCLC.
Two cytotoxic analogs, paclitaxel-octreotide (PTX-OCT) and 2paclitaxel-octreotide (2PTX-OCT), were synthesized by linking one or two molecules of paclitaxel to one molecule of somatostatin analog octreotide. PTX-OCT and 2PTX-OCT significantly inhibited the growth and induced apoptosis of SSTR2- and SSTR5-positive A549 cells, compared with the control (p < 0.01), and had less inhibitory effect on SSTR2- and SSTR5-negative H157 cells than paclitaxel (p < 0.01).
Moreover, compared with paclitaxel, PTX-OCT conjugates induced lower expression of MDR-1 gene both in vitro and in vivo.
Three A549 paclitaxel-resistant cell lines were established through different approaches, and the paclitaxel-resistant cell showed higher sensitivity to PTX-OCT conjugates than to paclitaxel, which might be because of the differential MDR-related gene expressions and cell-cycle distribution in paclitaxel-resistant A549 cells.
Our results suggested that PTX-OCT conjugates could be potentially used for SSTRs-mediated targeted therapy for NSCLC, especially for those with paclitaxel resistance and induced less multidrug resistance.
See also:
- Official Web Site: The Di Bella Method;
- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);
- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;
- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);
- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);
- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);
- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);
- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);
- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;
- Complete objective response to biological therapy of plurifocal breast carcinoma;
- Neuroblastoma: Complete objective response to biological treatment;
- Oesophageal squamocellular carcinoma: a complete and objective response.