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The strong interference suffered by users can be a severe problem in cache-enabled networks (CENs) due to the content-centric user association mechanism. To tackle this issue, multi-antenna technology may be employed for interference management. In this paper, we consider a user-centric interference nulling (IN) scheme in two-tier multi-user multi-antenna CEN, with a hybrid most-popular and random caching policy at macro base stations (MBSs) and small base stations (SBSs) to provide file diversity. All the interfering SBSs within the IN range of a user are requested to suppress the interference at this user using zero-forcing beamforming. Using stochastic geometry analysis techniques, we derive a tractable expression for the area spectral efficiency (ASE). A lower bound on the ASE is also obtained, with which we then consider ASE maximization, by optimizing the caching policy and IN coefficient. To solve the resultant mixed integer programming problem, we design an alternating optimization algorithm to minimize the lower bound of the ASE. Our numerical results demonstrate that the proposed caching policy yields performance that is close to the optimum, and it outperforms several existing baselines.