Histone deacetylase inhibitor pre-treatment enhances the efficacy of DNA-interacting chemotherapeutic drugs in gastric cancer

doi:10.3748/wjg.v26.i6.598

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World Journal of Gastroenterology

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1007-9327

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World J Gastroenterol. Feb 14, 2020; 26(6): 598-613
Published online Feb 14, 2020. doi: 10.3748/wjg.v26.i6.598

Table 2 Regime-specific synergistic, additive or antagonistic effects of chemotherapeutic drugs and histone deacetylase inhibitors

Drugs	Treatment sequence and result of FA and median effect plot analysis		FA
Drugs			0.5	0.75	0.95
Cisplatin and VPA	Pre	Dose of Cis, VPA (µmol/L)	0.965, 386.359	2.711, 1084.65	15.361, 6144.61
	Pre	CI	0.352	0.471	0.784
	Concurrent	Dose of Cis, VPA (µmol/L)	0.705, 282.387	3.874, 1549.74	67.690, 27076.0
	Concurrent	CI	0.257	0.673	3.454
	Post	Dose of Cis, VPA (µmol/L)	3.254 ,1301.90	9.362, 3745.16	55.260, 22104.1
	Post	CI	1.188	1.627	2.820
Oxaliplatin and VPA	Pre	Dose of Oxa, VPA (µmol/L)	0.788, 394.469	2.094, 1047.04	10.796, 5398.39
	Pre	CI	0.404	0.453	0.552
	Concurrent	Dose of Oxa, VPA (µmol/L)	1.533, 766.633	4.305, 2152.92	24.406, 12203.2
	Concurrent	CI	0.786	0.933	1.249
	Post	Dose of Oxa, VPA (µmol/L)	2.362, 1181.47	8.451, 4225.64	71.917, 35958.6
	Post	CI	1.211	1.83182	3.68265
Epirubicin and TSA	Pre	Combined dose (µg)	0.030, 0.300	0.093, 0.931	0.623, 6.231
	Pre	CI	0.645	0.727	1.222
	Concurrent	Combined dose (µg)	0.129, 1.299	0.410, 4.105	2.835, 28.356
	Concurrent	CI	2.789	3.207	5.563
	Post	Combined dose (µg)	0.137, 1.375	0.301, 3.010	1.122, 11.220
	Post	CI	2.952	2.351	2.201

FA: Fraction affected; Pre: Pre-treatment; Post: Post-treatment; TSA: Trichostatin A; Cis: Cisplatin; VPA: Valproic acid; Oxa: Oxaliplatin; CI: Combination index. Dose at Fa-0.5 for VPA- 1827.79, TSA-1.50, Cisplatin-6.84, Oxaliplatin-4.18 and Epirubicin- 0.07; Dose at Fa-0.75 for VPA- 4165.97, TSA-2.61, Cisplatin-12.85, Oxaliplatin-10.33 and Epirubicin- 0.25; Dose at Fa 0.95 for VPA- 16628.5, TSA-6.56, Cisplatin-37.06, Oxaliplatin-47.30, and Epirubicin- 2.29.

Citation: Amnekar RV, Khan SA, Rashid M, Khade B, Thorat R, Gera P, Shrikhande SV, Smoot DT, Ashktorab H, Gupta S. Histone deacetylase inhibitor pre-treatment enhances the efficacy of DNA-interacting chemotherapeutic drugs in gastric cancer. World J Gastroenterol 2020; 26(6): 598-613
URL: https://www.wjgnet.com/1007-9327/full/v26/i6/598.htm
DOI: https://dx.doi.org/10.3748/wjg.v26.i6.598