in vivo
GSK2643943A (5 mg/kg, i.p., daily, for 6 days) potentiates oHSV-1-induced oncolysis in SCC9 tumors[2].
GSK2643943A (2.5 mg/kg, i.p., daily, for 9 days) plays a regulatory role in oHSV-1 T1012G replication and oncolysis in SCC7 cells[2].
| Animal Model: | The subcutaneous xenograft model[2].
(SCC9 or SCC7 cells (8×106 cells or 1×106 cells), 5-week-old, female, BALB/c nude mice or C3H/HeN mice, four groups, n = 6-7, per group)[2] |
| Dosage: | 5 mg/kg |
| Administration: | GSK2643943A (alone): intraperitoneal administration, daily, for 6 days.
GSK2643943A (combination): intraperitoneal administration, daily for 6 days + intratumoral injection with 50 mL of 1×106 PFU T1012G in PBS on day 1, day 4, and day 7.
|
| Result: | Caused a visible drop of tumor volumes and significantly reduced the tumor volumes in mice with combined treatment of GSK2643943A and oHSV-1 T1012G.
Increased slightly viral ICP0 and gD mRNA accumulation in SCC9 tumors.
|
| Animal Model: | The SCC7 mouse model[2]. |
| Dosage: | 2.5 mg/kg |
| Administration: | GSK2643943A (alone): intraperitoneal administration, daily, for 9 days.
GSK2643943A (combination): intraperitoneal administration, daily, for 9 days + intratumoral injection, with 50 mL of 1×107 PFU T1012G in PBS on days 1, 4, 7, and 10.
|
| Result: | Caused a visible drop of tumor volumes, significantly reduced in mice with combined treatment of GSK and oHSV-1 T1012G.
Increased slightly viral ICP0 and gD mRNA accumulation in SCC7 tumors.
|
References
[1] Nishi Kumari, et al. Targeting the Ubiquitin Proteasome System in Cancer. Shahzad, Hafiz Naveed (2018). Neoplasm Targeting the Ubiquitin Proteasome System in Cancer. , 10.5772/intechopen.69560(Chapter 8).
[2] Ruitao Lu, et al. USP18 and USP20 restrict oHSV-1 replication in resistant human oral squamous carcinoma cell line SCC9 and affect the viability of SCC9 cells. Mol Ther Oncolytics. 2021 Nov 11;23:477-487. DOI:
10.1016/j.omto.2021.11.004