A novel inhibitor of Rho GDP-dissociation inhibitor α improves the therapeutic efficacy of paclitaxel in Lewis lung carcinoma

Abstract

Abstract. Molecular-targeted therapies are considered a promising strategy for the treatment of most types of human cancer. Rho GDP-dissociation inhibitor α (RhoGDIα), which functions mainly by controlling the cellular distribution and activity of Rho GTPases and is associated with tumor progression and poor prognosis of cancer patients, has become a new promising target for anticancer treatment. Recently, a specific RhoGDIα inhibitor (no. SKLB-163) was developed via computer-aided drug design and de novo synthesis. Previous studies have shown that SKLB-163 had extremely good antitumor activities against diverse cancer cell lines. In the present study, SKLB-163 was used in combination with paclitaxel in order to determine the synergistic effect of the antitumor activity. The findings showed that the combination therapy clearly inhibited cell proliferation and induced apoptosis of LL/2 in vitro. The LL/2 mice model also showed that the combination therapy inhibited tumor growth in vivo. Proliferative cell nuclear antigen (PCNA) immunohistochmeistry and terminal deoxynucleotidyl transferase dUTP nick end-labeling showed that combination therapy inhibited cell proliferation and increased apoptosis compared to the treatment with SKLB-163 or paclitaxel alone. The data suggests that the combination therapy exerted synergistic antitumor effects, providing a novel way to augment the antitumor efficacy of cytotoxic chemotherapy.

C60 fullerene enhances cisplatin anticancer activity and overcomes tumor cell drug resistance

“…Lewis lung carcinoma (LLC) is widely used as an experimental murine tumor model for evaluation of the efficiency of novel anticancer therapies [8,29,[69][70][71][72][73][74]. Consequently, we used this well-established tumor model to test our novel drug formulations as well.…”

Synergetic effect of high dose rate radiations (10× FFF/2400 MU/min/10 MV x‐rays) and paclitaxel selectively eliminates melanoma cells

“…Paclitaxel (microtubules disassembly protector, blocks the progression of mitosis and triggers apoptosis) was introduced in cancer therapy decades ago and has been widely used for ovarian, 7 , 8 , 9 , 10 breast, 11 , 12 Kaposi‐Sarcoma (AIDS‐related) 13 , 14 , 15 and lung carcinomas as a single agent or in combination with other drugs. 16 , 17 , 18 , 19 , 20 In multiple studies, Paclitaxel was investigated for its effectiveness in treating metastatic melanoma either as a single agent or in combination with small molecule inhibitors 21 and carboplatin 22 , 23 , 24 or immune‐cytokine F8‐IL2. 25 For non‐resection metastatic melanoma, Paclitaxel is currently in a clinical trial for first‐line therapy with other chemotherapy drugs with reporting promising primary results.…”

Combination of High Dose Rate Radiations (10X FFF/2400 MU/min/10 MV X-rays) and Paclitaxel Selectively Eliminates Melanoma Cells

“…Paclitaxel (microtubules disassembly protector, blocks the progression of mitosis and triggers apoptosis) was introduced in cancer therapy decades ago and has been widely used for ovarian [7][8][9][10], breast [11,12], Kaposi-Sarcoma (AIDS-related) [13][14][15] and lung carcinomas as a single agent or in combination with other drugs [16][17][18][19][20]. In multiple studies paclitaxel was investigated for its effectiveness to treat metastatic melanoma either as single agent or in combination with a small molecule inhibitor [21] small molecule inhibitors and carboplatin [22][23][24] or immunocytokine F8-IL2 [25].…”